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: Introduction: Dolutegravir‐based antiretroviral therapy (ART) is the preferred antiretroviral treatment for children and adolescents living with HIV. A large surveillance study in Botswana previously raised concerns about an association between pre‐conception dolutegravir and neural tube defects. Before these concerns were subsequently resolved, we set up a sub‐study to look at the effect of dolutegravir on levels of folate and vitamin B12 in children and adolescents within the randomized ODYSSEY trial, as folate and vitamin B12 are known to play a crucial role in neural tube development. Methods: We conducted the sub‐study among Ugandan ODYSSEY participants and compared folate and vitamin B12 between children randomized to dolutegravir‐based ART (DTG) and non‐dolutegravir‐based standard‐of‐care treatment (SOC). Plasma folate was measured at enrolment and week 4 on stored samples; in addition, plasma and red blood cell (RBC) folate and vitamin B12 were assayed at week ≥96 in prospectively collected samples. RBC mean corpuscular volume (MCV) was measured 24‐weekly in all ODYSSEY participants. Samples analysed in the sub‐study were collected between September 2016 and October 2020. Results: A total of 229 children aged ≥6 years were included in the sub‐study with median age at trial enrolment of 12.3 (interquartile range [IQR] 9.0, 14.7) years, and CD4 count of 501 (IQR 228, 695); 112 (49%) children were male. Most participants (225/229, 98%) had plasma folate results at enrolment and 214 (93%) children had results available for RBC folate, vitamin B12 and plasma folate at week ≥96. MCV results were analysed on 679 children aged ≥6 years enrolled in ODYSSEY. At week 4, mean plasma folate was significantly higher in the dolutegravir arm than in SOC (difference [DTG‐SOC] 1.6 ng/ml, 95% CI 0.8, 2.3; p Conclusions: Plasma and RBC folate levels were higher in children and adolescents receiving dolutegravir‐based ART than on other ART regimens. Further studies are needed to clarify the mechanisms of these interactions and the clinical implications of increased blood folate levels., INTRODUCTION Dolutegravir‐based antiretroviral therapy (ART) has become the preferred treatment option for children living with HIV due to superior efficacy and similar safety compared to non‐dolutegravir‐based ART [1]. A number [...]

Background Hemolytic uremic syndrome (HUS) is a clinical syndrome characterized by hemolytic anemia, thrombocytopenia, and acute kidney injury. Atypical hemolytic uremic syndrome (aHUS) is a devastating disease with significant mortality and high risk of progression to end-stage kidney disease. It is mostly caused by dysregulation of the alternative complement pathway. Cobalamin C (Cbl C) defect is a genetic disorder of cobalamin metabolism and is a rare cause of HUS. Case-diagnosis/treatment We present a 6-month-old male infant who was admitted to the pediatric intensive care unit (PICU) due to restlessness, severe hypertension, anemia, respiratory distress, and acute kidney injury. Metabolic screening revealed elevated plasma homocysteine levels, low methionine levels, and methylmalonic aciduria, and the patient was diagnosed as having HUS secondary to Cbl C defect. Additionally, complement factor H (CFH) and complement C3 levels were decreased. The infant was treated with betaine, hydroxycobalamin, and folic acid. After treatment, the homocysteine and methylmalonic acid levels were normalized but hemolysis and acute kidney failure persisted. He required continued renal replacement treatment (CRRT) and plasma exchange due to thrombotic microangiopathy (TMA). Therefore, we considered a second mechanism in the pathogenesis as complement dysregulation and gave eculizumab to the patient. After eculizumab treatment, the renal and hematologic indices improved and he was free of dialysis. Conclusions To the best of our knowledge, our patient is the first to have Cbl C defect-HUS accompanied by complement dysregulation, who responded well to eculizumab therapy., Author(s): Ulkem Kocoglu Barlas [sup.1] , Hasan Serdar Kihtir [sup.1] , Nilufer Goknar [sup.2] , Melike Ersoy [sup.2] , Nihal Akcay [sup.1] , Esra Sevketoglu [sup.1] Author Affiliations: (Aff1) Pediatric [...]

Background/objectives: Observationally, homocysteine is positively associated with ischemic heart disease (IHD) and unhealthy lipids; folate and vitamin B12, which reduce homocysteine, are associated with lower IHD risk and healthy lipids. Randomized controlled trials have shown no benefits of folate and vitamin B12 for IHD. To clarify the role of these potential targets of intervention in IHD we assessed how genetically determined homocysteine, folate and vitamin-B12-affected IHD and lipids. Subjects/methods: Separate-sample instrumental variable analysis with genetic instruments, that is, Mendelian randomization, was used to obtain unconfounded estimates (based on strongly related single-nucleotide polymorphisms (SNPs)) using CARDIoGRAMplusC4D, a large coronary artery disease/myocardial infarction (CAD/MI) case (n=64 374)-control (n=130 681) study with extensive genotyping, and the Global Lipids Genetics Consortium Results (n=196 475). Results: Homocysteine was unrelated to CAD/MI (odds ratio (OR) 1.07 per log-transformed s.d., 95% confidence interval (CI) 0.96 to 1.19) based on 14 SNPs, as was folate (OR 1.18 per s.d., 95% CI 0.80 to 1.75) based on rs153734, and vitamin B12 (OR 0.98 per log-transformed s.d., 95% CI 0.85 to 1.14) based on rs602662, rs9473555, rs526934 and rs11254363. Homocysteine and folate were not clearly associated with lipids, vitamin B12 was associated with higher inverse normal transformed low-density lipoprotein cholesterol (0.07, 95% CI 0.02 to 0.12) and triglycerides (0.05, 95% CI 0.004 to 0.09). Conclusions: Our findings do not corroborate the observed positive association of homocysteine or negative associations of folate and vitamin B12 with CAD/MI. Vitamin B12 might be associated with an unfavorable lipid profile., Author(s): J V Zhao [sup.1] , C M Schooling [sup.1] [sup.2] Author Affiliations: (1) School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong [...]

Author(s): Jean Daniel Delbet [sup.1] [sup.2] [sup.3] , Tim Ulinski [sup.1] [sup.2] [sup.3] Author Affiliations: (Aff1) 0000 0001 2175 4109, grid.50550.35, Pediatric Nephrology, Armand Trousseau Hospital, Assistance publique-Hôpitaux de Paris, [...]

Undernutrition as well as low levels of vitamin B12 and folic acid are common problems among older adults. However, recommended routine nutritional status assessment tools may result in inadequate vitamin serum levels to go unnoticed. Therefore, the aim of this study is to evaluate the inadequacy of serum levels of vitamin B12 and folic acid within Mini Nutritional Assessment (MNA) classification categories among older adults. A cross-sectional study was conducted with 97 older adults residing in care homes in Portugal. Undernutrition was identified through the MNA, and serum levels of vitamin B12 and folic acid were measured using chemiluminescence. Cognitive function, depressive symptoms and functional characteristics were also assessed using the Abbreviated Mental Test Score, the Epidemiologic Studies Depression Scale and the Barthel Index, respectively. The mean age of older adults was 82.2 (6.3) years; 3.1% were undernourished and 26.8% were at undernutrition risk. In the MNA normal nutritional status group, 11.8% presented vitamin B12 deficiency (< 200 pg/ml), 32.4% had low serum levels (200-400 pg/ml) and 4.4% had folic acid deficiency (< 3 ng/ml). A high proportion of older adults with low serum levels of vitamin B12 presenting normal nutritional status by MNA was identified. This finding emphasizes the need to evaluate serum vitamin B12 levels, independently of the MNA results. European Journal of Clinical Nutrition (2016) 70, 859-862; doi: 10.1038/ejcn.2016.33; published online 23 March 2016, INTRODUCTION Undernutrition is a common problem that affects older adults living in care homes. (1) A multinational study using Mini Nutritional Assessment (MNA) among older people living in nursing homes [...]

Between 1945 and 1959 it was convincingly documented that folic acid can precipitate or aggravate the neurological and haematological consequences of vitamin B12 deficiency by increasing the demand for vitamin B12. Since then there has been much misunderstanding of the issues, mainly by advocates of folic acid fortification who have been inclined to minimise or even dismiss the risks by misinterpreting the evidence as only a 'masking' of the anaemia of pernicious anaemia. Recent studies in the era of fortification are rediscovering the risks to the nervous system, especially cognitive function, of excess folate in the presence of vitamin B12 deficiency. I have reviewed the Reports of four Expert Advisory Committees in Europe and the USA, which suggest that the safe upper tolerable limit (UL) for folic acid is 1 mg in adults. These reports are unsound and there is already evidence of neurological harm from long-term exposure to doses of folic acid between 0.5 and 1 mg in the presence of vitamin B12 deficiency. There is an urgent need to review the safe UL for folic acid and to consider the addition of vitamin B12 to folic acid fortification policies. European Journal of Clinical Nutrition (2016) 70, 537-540; doi: 10.1038/ejcn.2015.231; published online 10 February 2016, INTRODUCTION During the late 1940s and the 1950s there were many reports that the newly discovered folic acid not only failed to prevent neurological deterioration in pernicious anaemia (PA) but [...]

BACKGROUND/OBJECTIVES: Depression can decrease quality of life and affect health outcomes in older population. We investigated whether different intake levels of folate, vitamin [B.sub.6] and [B.sub.12] were associated with a 3-year depression incidence among generally healthy, community-dwelling older men and women. SUBJECTS/METHODS: Participants in the Quebec Longitudinal Study on Nutrition and Aging (NuAge), free of depression (that is, 30-item Geriatric Depression Scale (GDS) < 11) at baseline (N = 1368; 74 [+ or -] 4 years old; 50.5% women), were screened annually for incident depression (GDS [greater than or equal to] 11) or antidepressant medication. Tertiles of intakes (food only and food + supplements) were obtained from the mean of three non-consecutive 24-h recalls at baseline. Sex-stratified multiple logistic regression models were adjusted for age, physical activity, physical functioning, stressful life events and total energy intake. RESULTS: Over 3 years, 170 participants were identified as depressed. Women in the highest tertile of [B.sub.6] intake from food were 43% less likely to become depressed when adjusting for demographic and health factors (multivariate odds ratio (OR) 0.57, 95% confidence interval (CI) 0.39-0.96), but adjustment for energy intake attenuated the effect. Men in the highest tertile of dietary [B.sub.12] intake had decreased risk of depression (energy-adjusted multivariate OR 0.42, 95% CI 0.20-0.90). No other association was observed. CONCLUSIONS: This study provides some evidence of decreased depression risk among women with higher intakes of vitamin [B.sub.6] from food, which was dependent on total energy intake, and among men with higher intakes of [B.sub.12] from food, independently of energy intake. European Journal of Clinical Nutrition (2016) 70, 380-385; doi: 10.1038/ejcn.2015.202; published online 9 December 2015, INTRODUCTION In patients with psychiatric disorders, including depression, higher prevalence rates of B-vitamin deficiency, particularly folate, [B.sub.6] and [B.sub.12], have been reported when compared with their healthy peers. (1,2) Although [...]

BACKGROUND/OBJECTIVES: Maternal nutrient supplementation in developing countries is generally restricted to provision of iron and folic acid. Along with folic acid, vitamin [B.sub.12] is also an important determinant of fetal growth and development. During pregnancy, the increased requirement of folic acid is met with supplementation, while vitamin [B.sub.12] remains untreated and possibly deficient. The objective of our study was to study the combined effect of maternal plasma folate and vitamin [B.sub.12], and their ratio on birth anthropometrics. SUBJECTS/METHODS: We carried out an observational study on 49 full-term pregnant women at KEM Hospital, Pune, India, during 2006-2008, and measured plasma folate, vitamin [B.sub.12] and homocysteine in venous blood at 36 weeks of gestation. Neonatal anthropometrics (birth weight, length, head circumference, abdominal circumference, mid arm circumference, chest circumference, triceps skinfold and subscapular skinfold thickness) were measured within 24 h of birth. RESULTS: Maternal plasma folate and vitamin [B.sub.12] were not correlated to neonatal anthropometrics. The combined association of folate and vitamin [B.sub.12] expressed as folate to vitamin [B.sub.12] ratio was correlated to the neonatal anthropometrics. Imbalance in the maternal micronutrients with increasing ratio of folate to vitamin [B.sub.12] was associated with an increase in plasma homocysteine (P = 0.014), lowering of neonatal birth weight (P = 0.009), birth length (P = 0.034), head circumference (P = 0.018) and chest circumference (P = 0.009), while no significant association to other anthropometrics was observed. CONCLUSIONS: Supplementation of vitamin [B.sub.12] in addition to supplementation of folic acid in pregnancy may be important for improving birth weight, birth length, head circumference and chest circumference. European Journal of Clinical Nutrition (2014) 68, 726-729; doi:10.1038/ejcn.2013.289; published online 22 January 2014 Keywords: folic acid; vitamin [B.sub.12]; homocysteine; pregnancy; birth weight; birth length, INTRODUCTION Pregnancy is associated with a higher requirement of energy, protein and micronutrients for the growth and development of the fetus. Supplementation of folic acid is recommended to prevent neural [...]

BACKGROUND/OBJECTIVES: Folate, pyridoxine and cobalamin are coenzymatically essential in one-carbon methyl metabolism, and their deficiencies could explain some alterations during breast carcinogenesis. We aimed to evaluate the validity of folate, pyridoxine and cobalamin estimates from a food frequency questionnaire (FFQ) on the basis of their corresponding fasting plasma biomarkers, in breast cancer (BC) patients. SUBJECTS/METHODS: In a prospective, consecutive case series, 149 women with primary BC aged between 30 and 69 years as a representative sample of Iranian women with BC were recruited. The 136-item FFQ was used for the validity assay. Fasting plasma folate and cobalamin were tested by automated electrochemiluminescence. The high-pressure liquid chromatography with fluorescence detection was used to determine the plasma levels of pyridoxal-5'-phosphate (PLP) and total homocysteine (tHcy). RESULTS: Area under the curve (AUC) for assessing the diagnostic accuracy of folate-related data through an FFQ was 0.74 (P CONCLUSIONS: Dietary folate and cobalamin estimates from FFQ were significantly correlated with their fasting plasma concentrations. Our data supported the validity of new FFQ to rank individuals by dietary intake status of folate and cobalamin. European Journal of Clinical Nutrition (2014) 68, 316-323;doi:10.1038/ejcn.2013.209; published online 30 October 2013 Keywords: food frequency questionnaire; folate; cobalamin; validation study; total homocysteine; breast cancer, INTRODUCTION Several lines of epidemiologic evidence and preclinical investigations have shown that diminished folate status in longitude could increase predominantly the risk of breast cancer (BC) carcinogenesis. (1-4) In addition, [...]

This review brings together human and animal studies and reviews that examine the possible role of maternal vitamin B12 (B12) on fetal growth and its programming for susceptibility to chronic disease. A selective literature review was undertaken to identify studies and reviews that investigate these issues, particularly in the context of a vegetarian diet that may be low in B12 and protein and high in carbohydrate. Evidence is accumulating that maternal B12 status influences fetal growth and development. Low maternal vitamin B12 status and protein intake are associated with increased risk of neural tube defect, low lean mass and excess adiposity, increased insulin resistance, impaired neurodevelopment and altered risk of cancer in the offspring. Vitamin B12 is a key nutrient associated with one carbon metabolic pathways related to substrate metabolism, synthesis and stability of nucleic acids and methylation of DNA which regulates gene expression. Understanding of factors regulating maternal-fetal one carbon metabolism and its role in fetal programming of non communicable diseases could help design effective interventions, starting with maternal nutrition before conception. European Journal of Clinical Nutrition (2014) 68, 2-7; doi: 10.1038/ejcn.2013.232; published online 13 November 2013 Keywords: vitamin B12; methyl donor; one-carbon metabolism; fetal growth; programming; chronic disease, INTRODUCTION Across the life course, the dietary supply of the methyl donors: folate, vitamin B12, betaine, methionine and choline, is essential for normal growth, development and physiological functions. One carbon [...]

Background/Objectives: Helicobacter pylori infection and iron and vitamin [B.sub.12] deficiencies are widespread in economically disadvantaged populations. There is emerging evidence that H. pylori infection has a negative effect on the absorption of these micronutrients. The aim of this study was to evaluate the effect of H. pylori infection on the efficacy of micronutrient (including iron and vitamin [B.sub.12])-fortified foods supplied for 1 year in marginally nourished children. Subjects/Methods: In all, 543 Indian children, aged 6-10 years, participated in a double-blind, randomized controlled intervention trial, receiving foods fortified with either high (100% Recommended Dietary Allowances (RDA)) or low (15% RDA) amounts of iron, vitamin [B.sub.12] and other micronutrients. The presence of H. pylori infection was diagnosed by the [sup.13]C-labeled urea breath test at 11 months after the start of the intervention. Blood hemoglobin, serum ferritin (SF), total body iron and plasma vitamin [B.sub.12] were estimated at baseline and 12 months, and differences between these time points were assessed using an independent t-test. Results: Overall, the prevalence of H. pylori infection in this group of children was 79%. Baseline hemoglobin, SF, body iron and vitamin [B.sub.12] concentrations were not associated with H. pylori infection. The response to the intervention (either high or low amounts of iron and vitamin [B.sub.12] fortification) in terms of change in iron markers and vitamin [B.sub.12] status did not differ between children with and without H. pylori infection. Conclusions: This study shows that the presence of H. pylori infection did not affect the efficacy of long-term iron and vitamin [B.sub.12] fortification in these marginally nourished children. doi: 10.1038/ejcn.2010.126; published online 4 August 2010 Keywords: H. pylori infection; iron deficiency; vitamin [B.sub.12]; micronutrients; children; India, Introduction Helicobacter pylori is a Gram-negative bacterium that colonizes the gastric mucosa in humans (Parsonnet, 1998; Sarker et al, 2004). Prevalence of H. pylori infection among developing country populations is [...]

Our aim in this longitudinal study was to determine predictors of folate and cobalamin status in infancy. Data were collected from 364 mother-infant pairs with blood measurements from pregnancy (~18 wk; n = 149), newborns (cord serum; n = 361), and 6-mo-old partially or exclusively breast-fed children (n = 221). Serum/plasma folate, cobalamin, holotranscobalamin (holoTC), holohaptocorrin (holoHC), methylmalonic acid (MMA) and total homocysteine (tHcy) at birth and 6 mo were related to maternal vitamin status, parity, lifestyle variables, and anthropometry. In multivariate analyses, the strongest predictors of folate at birth and 6 mo were maternal folate and cord folate, respectively (P < 0.01). Maternal holoTC best predicted cobalamin status at birth (positively associated with cord cobalamin, holoTC, and holoHC; inversely with MMA and tHcy; P [less than or equal to] 0.001), whereas maternal and cord holoHC were the strongest predictors of cobalamin status at 6 mo (positively associated with cobalamin, holoTC, holoHC; inversely with tHcy; P < 0.05). The association between cobalamin status and parity was negative at birth but positive at 6 mo. Birth weight, female sex, and smoking were associated with low cobalamin or high tHcy at birth but showed no or opposite associations at 6 mo. In conclusion, maternal folate and cobalamin status exerts a long-term positive effect on infant vitamin status. The effect of smoking, parity and female sex on cobalamin status did not persist beyond the newborn period. Maternal holoTC was the superior predictor of newborn cobalamin status, while holoHC could be a valuable marker for predicting cobalamin status later in infancy. doi: 10.3945/jn.109.117424.

Background: While the majority of cases of nutritional anemia in developing countries are caused by iron deficiency, other micronutrient deficiencies may also be involved. In Colombia, it was recently reported that 38% of school children were anemic; yet, the rate of iron deficiency was only 3.6%. Objective: To determine if micronutrients other than iron were responsible for low hemoglobin concentrations in Colombian school children. Methods: We examined hemoglobin concentrations in relation to plasma ferritin, vitamin A, vitamin B12, and erythrocyte folate levels in a representative sample of 2812 low--and middle-income children (5-12 years) from Bogota, Colombia. Results: In multivariate analysis, hemoglobin concentration was positively associated with child&apos;s age, mother&apos;s age, household&apos;s socioeconomic stratum, and family income. Low ferritin was related to 3.6g/l lower hemoglobin concentration (95% confidence interval =-6.0, -1.3). Unexpectedly, we found an inverse trend in hemoglobin concentration by quartiles of erythrocyte folate; the adjusted hemoglobin concentration difference between the highest and lowest folate quartiles was -6.0g/l (95% confidence interval=-7.2, -4.9; P for trend 221 pmol/l (-5.7g/l); P for interaction=0.04. Conclusions: Hemoglobin concentration is inversely related to erythrocyte folate concentrations in a setting where folate fortification was adopted more than a decade ago. The impact of improving vitamin B12 status on this inverse relationship should be examined. doi:10.1038/ejcn.2008.50; published online 29 October 2008 Keywords: hemoglobin; folate; vitamin B12; school children, Introduction Anemia is a widespread problem in developing countries, affecting approximately 50% of school children (WHO/ UNICEF/UNU, 2001). The consequences of anemia include poor school performance, reduced work capacity, increased [...]

Background/Objectives: Folate and vitamin B12 have been suggested to play a role in chronic diseases like cardiovascular diseases. The objectives are to give an overview of the actual intake and status of folate and vitamin 1312 in general populations in Europe, and to evaluate these in view of the current vitamin recommendations and the homocysteine concentration. Methods: Searches in Medline with &apos;folic acid&apos;, &apos;folate&apos; and &apos;vitamin 1312&apos;, &apos;1312&apos; or &apos;cobalamin&apos; as key words were combined with the names of the European countries. Populations between 18 and 65 years were included. Results: Sixty-three articles reporting on studies from 15 European countries were selected. Low folate intakes were observed in Norway, Sweden, Denmark and the Netherlands. Low intakes of vitamin B12 were not common and only seen in one small Greek study. In the countries with a low intake of folate, the recommended levels were generally not achieved, which was also reflected in the folate status. Vitamin 1312 intake was not strongly associated with the vitamin 1312 status, which can explain why in the Netherlands and Germany the vitamin 1312 status was inadequate, despite sufficient intake levels. In countries with a low folate intake in particular, the Hcy concentration was higher than ideal. Conclusions: Populations from the Nordic countries, the Netherlands, Germany and Greece may need to improve their intakes of folic acid, 1312 or both to either meet the recommendations or to optimize their statuses. This could be achieved via a food-based approach, food fortification or supplements. doi:10.1038/sj.ejcn.1602897; published online 12 September 2007 Keywords: folic acid; folate; vitamin B12; homocysteine; vascular disease, Introduction Much attention has been given to B-vitamins, in particular to folate and vitamin B12, because of their potential influence on cardiovascular diseases (CVD) (Folsom et al., 1998; Rimm et [...]

Background Estimates of dietary folate and vitamin B-12 intakes are currently of considerable interest, but a valid assessment method that is faster than those currently available would better suit everyday health promotion activities. Objective To validate a new assessment technique for estimating folate and vitamin B-12 intakes, known as the Food Choice Map (FCM), using serum folate and vitamin B-12 concentrations in a group of 95 women aged 18 to 25 years. Design The FCM tool was used in a cross-sectional study design to estimate the usual folate and vitamin B-12 intakes of each participant. Immediately thereafter, blood samples were taken to determine serum folate and vitamin B-12 concentrations. Subsequently, 3-day food records were completed during each of three successive weeks and used as the reference method. Using the method of triads, validity coefficients were calculated. Results There was no significant difference between the two methods in the correlations with serum values. FCM-obtained folate intakes (r=0.43, P<0.01) exhibited a similar and moderate association with serum folate as did 3-day food record-obtained folate intakes (r=0.39, P<0.01). Similarly, vitamin B-12 intakes obtained from both techniques showed a modest association with serum vitamin B-12 (FCM r=0.40, P<0.01; 3-day food record r=0.44, P < 0.01 ). However, the validity coefficient for the FCM was higher than that for the 3-day food record for both folate (FCM 0.97, 3-day food record 0.79) and B-12 (FCM 0.95; 3-day food record 0.85). Conclusions This study provides validation for the use of a new dietary assessment method, the FCM, for estimating folate and vitamin B-12 intakes in women of reproductive age. Larger validation studies that include men and other age groups are needed to further characterize the applicability of the FCM.

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.jada.2008.09.002 Byline: Aysheh M. Shuaibi, Gustaaf P. Sevenhuysen, James D. House Abstract: Estimates of dietary folate and vitamin B-12 intakes are currently of considerable interest, but a valid assessment method that is faster than those currently available would better suit everyday health promotion activities. Article History: Accepted 13 June 2008

The study aims to examine the effect of a combination of folic acid, Vitamin B6, and Vitamin B12 on cancer risk in women found to be at high risk of cardiovascular disease. The results indicate that combination of folic acid, Vitamin B6, and Vitamin B12 had no significant effect on the risk of cancer in women.

The etiology of anemia during pregnancy in rural Southern Ethiopia is uncertain. Intakes of animal-source foods are low and infections and bacterial overgrowth probably coexist. We therefore measured the dietary intakes of a convenience sample of Sidama women in late pregnancy who consumed either maize (n = 68) or fermented enset (Enset ventricosum) (n = 31) as their major energy source. Blood samples were analyzed for a complete blood count, vitamin B-12 and folate status, plasma ferritin, retinol, zinc, albumin, and C-reactive protein (CRP). The role of infection and gravida was also examined. Dietary intakes were calculated from 1-d weighed records. No cellular animal products were consumed. Of the women, 29% had anemia, 13% had iron deficiency anemia, 33% had depleted iron stores, and 74 and 27% had low plasma zinc and retinol, respectively. Only 2% had low plasma folate ( 271 nmol/L). None had elevated plasma cystathionine or total homocysteine (tHcys). Women with enset-based diets had higher (P = 0.052) plasma vitamin B-12 concentration and lower (P < 0.05) cell volume, plasma cystathionine, and retinol than women consuming maize-based diets, but mean hemoglobin, plasma ferritin, MMA, tHcys, and folate did not differ. Plasma zinc, followed by CRP ([greater than or equal to] 5 mg/L), gravida ([greater than or equal to] 4), and plasma ferritin ([less than or equal to]12 [micro] g/L) status were major positive predictors of hemoglobin. Despite some early functional vitamin B-12 deficiency, there was no macrocytic anemia. Consumption of fermented enset may have increased vitamin B-12 levels in diet and plasma.

Background/Objectives: The available evidence from randomised controlled trials suggests that vitamin B12 supplementation does not improve neurologic function in older people with marginal but not deficient Vitamin B12 status. This secondary analysis used data from the Older People and Enhanced Neurological function (OPEN) randomised controlled trial to assess whether baseline vitamin B12 status or change in vitamin B12 status over 12 months altered the effectiveness of dietary vitamin B12 supplementation on neurologic function in asymptomatic older people with depleted vitamin B12 status at study entry. Subjects/Methods: Vitamin B12 status was measured as serum concentrations of vitamin B12, holotranscobalamin, homocysteine and via a composite indicator (cB12). Neurological function outcomes included eleven electrophysiological measures of sensory and motor components of peripheral and central nerve function. Linear regression analyses were restricted to participants randomised into the intervention arm of the OPEN trial (n=91). Results: Analyses revealed an inconsistent pattern of moderate associations between some measures of baseline vitamin B12 status and some neurological responses to supplementation. The directions of effect varied and heterogeneity in effect across outcomes could not be explained according to type of neurological outcome. There was no evidence of differences in the neurological response to vitamin B12 supplementation according to change from baseline over 12 months in any indicator of B12 status. Conclusions: This secondary analysis of high-quality data from the OPEN trial provides no evidence that baseline (or change from baseline) vitamin B12 status modifies the effect of vitamin B12 supplementation on peripheral or central nerve conduction among older people with marginal vitamin B12 status. There is currently insufficient evidence of efficacy for neurological function to support population-wide recommendations for vitamin B12 supplementation in healthy asymptomatic older people with marginal vitamin B12 status. European Journal of Clinical Nutrition (2017) 71, 1166-1172; doi: 10.1038/ejcn.2017.7; published online 22 February 2017, Author(s): L M Miles [1]; E Allen [1]; R Clarke [2]; K Mills [3]; R Uauy [1]; A D Dangour [1] Introduction Ageing is associated with a decline in vitamin [...]

Background/Objectives: Vitamin B[sub.12] deficiency during pregnancy has been associated with increased risk of adverse perinatal outcomes. However, few studies have investigated the burden and determinants of vitamin B[sub.12] status in young infants. This study was conducted to determine the associations between maternal and infant vitamin B[sub.12] status. Subjects/Methods: Pregnant women participating in a vitamin B[sub.12] supplementation trial in Bangalore, India, were randomized to receive vitamin B[sub.12] (50 [mu]g) or placebo supplementation daily during pregnancy through 6 weeks postpartum. All women received 60 mg of iron and 500 [mu]g of folic acid daily during pregnancy, as per standard of care. This prospective analysis was conducted to determine the associations between maternal vitamin B[sub.12] biomarkers (that is, plasma vitamin B[sub.12], methylmalonic acid (MMA) and tHcy) during each trimester with infant vitamin B[sub.12] status (n=77) at 6 weeks of age. Results: At baseline ([precedes/equal to]14 weeks of gestation), 51% of mothers were vitamin B[sub.12] deficient (vitamin B[sub.12] [less than] 150 pmol/l) and 43% had impaired vitamin B[sub.12] status (vitamin B[sub.12] [less than] 150 pmol/l and MMA [greater than] 0.26 [mu]mol/l); 44% of infants were vitamin B[sub.12] deficient at 6 weeks of age. After adjusting for vitamin B[sub.12] supplementation, higher vitamin B[sub.12] concentrations in each trimester were associated with increased infant vitamin B[sub.12] concentrations and lower risk of vitamin B[sub.12] deficiency in infants (P [less than] 0.05). After adjusting for vitamin B[sub.12] supplementation, infants born to women with vitamin B[sub.12] deficiency had a twofold greater risk of vitamin B[sub.12] deficiency (P [less than] 0.01). Higher maternal folate concentrations also predicted lower risk of vitamin B[sub.12] deficiency in infants (P [less than] 0.05). Impaired maternal vitamin B[sub.12] status, which combined both circulating and functional biomarkers, was the single best predictor of infant vitamin B[sub.12] status. Conclusions: Impaired maternal vitamin B[sub.12] status throughout pregnancy predicted higher risk of vitamin B[sub.12] deficiency in infants, after adjusting for vitamin B[sub.12] supplementation. Future interventions are needed to improve vitamin B[sub.12] status periconceptionally, and to ensure optimal vitamin B[sub.12] status and health outcomes in pregnant women and their children. European Journal of Clinical Nutrition (2017) 71, 1046-1053; doi: 10.1038/ejcn.2017.29; published online 12 April 2017, Author(s): J L Finkelstein [1, 2]; A V Kurpad [2, 3]; T Thomas [4]; K Srinivasan [5, 6]; C Duggan [2, 7] Introduction Vitamin B[sub.12] deficiency is a major threat [...]

Adequate folate availability is necessary to sustain normal DNA synthesis and normal patterns of DNA methylation and these features of DNA can be modified by methylenetetrahydrofolate reductase (MTHFR) C677T genotype. This study investigated the effect of MTHFR C677T genotype and daily supplementation with 5 mg folic acid and 1.25 mg vitamin B-12 on uracil misincorporation into DNA and promoter methylation. Subjects (n = 86) with a history of colorectal adenoma and MTHFR CC or TT genotype were randomly assigned to receive folic acid plus vitamin B-12 or placebo for 6 mo. Uracil misincorporation and promoter methylation of 6 tumor suppressor and DNA repair genes were assessed in DNA from rectal biopsies at baseline and after the intervention. The biomarkers did not differ between the treated group and the placebo group after 6 mo compared with baseline. The uracil concentration of DNA increased in the treated group (5.37 fmol/[micro]g DNA, P = 0.02), whereas it did not change in the placebo group (P = 0.42). The change from baseline of 4.01 fmol uracil/[micro]g DNA tended to differ between the groups (P = 0.16). An increase in promoter methylation tended to occur more often in the intervention group than in the placebo group (OR = 1.67; P = 0.08). This study suggests that supplementation with high doses of folic acid and vitamin B-12 may not favorably influence uracil incorporation and promoter methylation in subjects with previous colorectal adenomas. Because such alterations may potentially increase the risk of neoplastic transformation, more research is needed to fully define the consequences of these molecular alterations.

Abstract Nail health and appearance are global concerns. We investigated the use of biotin vitamin E, alpha-tocopherol, vitamin C (ascorbic acid), vitamin A, retinoids, retinol, retinal, silicon, zinc, iron, copper, [...]

The growth of Dehalococcoides ethenogenes 195 is described in a defined mineral salts medium, improved growth of strain 195 when the medium is amended with high concentrations of vitamin [B.sub.12]. The growth of D. ethenogenes strain 195 in defined medium is optimized by providing high concentrations of vitamin [B.sub.12].

The high prevalence of vitamin B-12 deficiency in many regions of the world is becoming recognized as a widespread public health problem, but it is not known to what extent this deficiency results from a low intake of the vitamin or from its malabsorption from food. In rural Kenya, where a previous study identified a high prevalence of inadequate vitamin B-12 intakes, this study examined whether plasma vitamin B-12 concentrations were associated with dietary sources of the vitamin at baseline and could be increased by supplementation with animal source foods (ASF). The 4 experimental groups in 503 school children were: 1) control (no food provided); 2) githeri (a maize and bean staple with added oil); 3) githeri + meat (githeri + minced beef); or 4) githeri + milk (githeri + milk). Feedings were isocaloric. Dietary data were collected at baseline, and biochemical data at baseline and after 1 and 2 y of feeding. Baseline plasma vitamin B-12 concentration was 193.6 [+ or -] 105.3 pmol/L and correlated with % energy from ASF (r = 0.308, P < 0.001). The odds ratio for low plasma vitamin B-12 (

Objective To evaluate the biopotency of the viable probiotic Lactobacillus acidophilus (La1) in yoghurt matrix consumed by Egyptian children on their plasma vitamin [B.sub.12] and folate levels, and their metabolic markers methylmalonic acid (MMA) and total homocysteine (t-Hcy). Methods A randomized nutritional supplementation trial (42 days duration) was performed in free-living children of both sexes (11 years old). The Lal in yoghurt matrix was administered to provide [10.sup.12] colony-forming units/subject/day. Blood sampling for the analysis of plasma vitamin [B.sub.12], folate and t-Hcy was performed by standardized methods. Five-hour urine collection was used for the analysis of MMA and t-Hcy. Results Initially 33.3% of the children presented with biochemical vitamin [B.sub.12] deficiency ( < 208 pg/ml), while one-fifth (21%) were biochemically deficient in folate ( < 3 ng/ml folate/ml plasma or 0.68 nmol/l). Fifty percent of the children presented with high plasma t-Hcy ( > 15.0 [micro]mol/1). The daily consumption of the probiotic La1 yoghurt for 42 days significantly improved the mean levels of plasma vitamin [B.sub.12] (P Keywords: Egyptian children, vitamin B12, folate, homocysteine, urinary methylmalonic acid, nutrition intervention, Lactobacillus acidophilus

There is a need for an improved test of human ability to assimilate dietary vitamin [B.sub.12]. Assaying and understanding absorption and uptake of [B.sub.12] is important because defects can lead to hematological and neurological complications. Accelerator mass spectro metry is uniquely suited for assessing absorption and kinetics of carbon-14 ([sup.14]C)-Iabeled substances after oral ingestion because it is more sensitive than decay counting and can measure levels of [sup.14]C in microliter volumes of biological samples with negligible exposure of subjects to radioactivity. The test we describe employs amounts of [B.sub.12] in the range of normal dietary intake. The [B.sub.12] used was quantitatively labeled with [sup.14]C at one particular atom of the dimethylbenzimidazole (DMB) moiety by exploiting idiosyncrasies of Salmonella metabolism. To grow aerobically on ethanolamine,Salmonella enterica must be provided with either preformed [B.sub.12] or two of its precursors, cobinamide and DMB. When provided with [sup.14]C-DMB specifically labeled in the C2 position, cells produced [sup.14]C-[B.sub.12] of high specific activity (2.1 GBq/ mmol, 58 mCi/mmol) (1Ci = 37 GBq) and no detectable dilution of label from endogenous DMB synthesis. In a human kinetic study, a physiological dose (1.5[micro]g, 2.2 kBq/59 nCi) of purified [sup.14] C-B.sub.12] was administered and showed plasma appearance and clearance curves consistent with the predicted behavior of the pure vitamin. This method opens new avenues for study of [B.sub.12] assimilation. dimethylbenzimidazole | ethanolamine | metabolic engineering | Salmonella | Schilling test

An insight into a previously unknown step in [B.sub.12] biosynthesis was unexpectedly obtained through our analysis of a mutant of the symbiotic nitrogen fixing bacterium Sinorhizobium meliloti. This mutant was identified based on its unusually bright fluorescence on plates containing the succinoglycan binding dye calcofluor. The mutant contains a Tn5 insertion in a gene that has not been characterized previously in S. meliloti. The closest known homolog is the bluB gene of Rhodobacter capsulatus, which is implicated in the biosynthesis of [B.sub.12] (cobalamin). The S. meliloti bluB mutant is unable to grow in minimal media and fails to establish a symbiosis with alfalfa, and these defects can be rescued by the addition of vitamin [B.sub.12] (cyanocobalamin) or the lower ligand of cobalamin, 5,6-dimethylbenzimidazole (DMB). Biochemical analysis demonstrated that the bluB mutant does not produce cobalamin unless DMB is supplied. Sequence comparison suggests that BluB is a member of the NADH/flavin mononucleotide (FMN)-dependent nitroreductase family, and we propose that it is involved in the conversion of FMN to DMB. cobalamin | symbiosis | bacteria | vitamin [B.sub.12] | biosynthesis

Objective: To examine the prevalence of low serum folate and vitamin B12, in association with elevated serum homocysteine, in a representative sample of older Australians. Methods: During 1997-2000, 3,508 persons aged 50+ years were examined in a population-based cohort study conducted in two postcodes, west of Sydney, Australia. Of these, 2,901 participants (82.7%) provided fasting blood for estimates of serum folate, vitamin B12 and total homocysteine. Results: Low serum B12 ( Conclusions: Low serum levels of vitamin B12 and elevated serum homocysteine are relatively frequent in older Australians. Implications: Appropriate public health action should be considered to reduce the prevalence of low serum vitamin B12 and elevated homocysteine in older Australians.

ABSTRACT Cobalamin deficiency may cause cognitive deficits and even dementia. In Alzheimer's disease, the most frequent cause of dementia in elderly persons, low serum levels of vitamin [B.sub.12], may be [...]

A well-planned vegetarian diet has been stated to be adequate during pregnancy. The aim of the present study was to compare serum vitamin B-12 and homocysteine concentrations in pregnant women (n = 109) consuming vegetarian and Western diets and to evaluate the adequacy of current dietary reference intakes of vitamin B-12 for these women. Pregnant women adhering to vegetarian diets for at least 3 y, with subgroups of ovo-lacto vegetarians (OLVs; n = 27), low-meat eaters (LME, n = 43), and women eating an average Western diet (control group, n = 39), were recruited. Dietary vitamin B-12 intake, serum vitamin B-12, and plasma total homocysteine (tHcy) concentrations were measured in wk 9-12, 20-22, and 36-38 of pregnancy. During pregnancy serum vitamin B-12 concentrations of ovo-lacto vegetarians (P < 0.001) and low-meat eaters (P = 0.050) were lower than those of the control group. We observed the combination of low serum vitamin B-12 concentrations and elevated plasma tHcy in 22% of ovo-lacto vegetarians, in 10% of low-meat eaters, and in 3% of controls (P = 0.003). In OLVs, serum vitamin B-12 predicted 60% of the plasma tHcy variation (P < 0.001), but in LMEs and controls only KEY WORDS: * pregnancy * vitamin B-12 * homocysteine * vegetarian diets

Objective: To determine whether combination therapy with lofepramine, L-phenylalanine, and intramuscular vitamin B-12 (the 'Cari Loder regime') reduces disability in patients with multiple sclerosis. Methods: A placebo controlled, double blind, [...]

Vitamin B therapy may prevent the progression of coronary artery disease in patients who have had angioplasty to open up blocked coronary arteries. In many patients, the arteries become blocked again within months. In a study of 553 patients, those who took folic acid, and vitamins B6 and B12 were less likely to need a second angioplasty compared to those who took a placebo, or inactive substance.

Methylenetetrahydrofolate reductase (MTHFR) polymorphisms may negatively influence one-carbon metabolism and increase health risks in women of reproductive age. The effect of MTHFR single nucleotide polymorphisms at bp 677 and/or 1298 and differences in folate and vitamin B-12 status on plasma homocysteine concentration in women of reproductive age (20-30 y; n = 186) were investigated. From the multivariate regression model, homozygotes (n = 23) for the C677T MTHFR variant had plasma homocysteine concentrations that were higher (P < 0.05) than those observed in the other 5 genotype groups, including those who were heterozygous for both variants (677CT/1298AC; n = 32). Plasma homocysteine was negatively associated with plasma vitamin B-12 concentration (P = 0.015) and serum folate (P = 0.049), with the degree of correlation between plasma vitamin B-12 and homocysteine concentrations dependent on MTHFR genotype. The C677T and A1298C MTHFR polymorphisms were significant predictors (P < 0.05) of plasma homocysteine when regression analysis was used to model plasma homocysteine concentration as a function of genotype, supplement use, serum folate and plasma vitamin B-12 concentration. Plasma homocysteine decreased as vitamin B-12 concentration increased (P = 0.0005) in individuals who were heterozygous for both the C677T and A1298C variants with nonsignificant trends (P = 0.114-0.128) in individuals homozygous for either the C677T or A1298C variants. In contrast, within the group of individuals with the wild-type genotype for both the C677T and A1298C MTHFR variants, homocysteine was not associated with changes in plasma vitamin B-12 concentrations. These data suggest that enhancing vitamin B-12 status may significantly decrease homocysteine in young women with C677T and/or A1298C MTHFR polymorphisms, even when vitamin B-12 concentrations are within the normal range. KEY WORDS: * vitamin B-12 * methylenetetrahydrofolate reductase * polymorphisms * homocysteine * folate * women

Nutritional factors are integrally linked with Alzheimer's disease (AD). Although AD patients have no changes in energy metabolism, fluctuations in weight are fairly common. The potential role of vitamin [B.sub.12] and folate, with the production of hyperhomocysteinemia, in the pathophysiology of AD is explored. The role of free-radical damage in AD is discussed. It is stressed that alterations in dietary lipids may play an important role in cognitive defects in AD secondary to their effects on neuronal membrane lipids. More research is needed on the role of nutrition in the ongoing development of cognitive changes in AD.

Byline: Rajesh. Gupta, Jagdish. Mandliya, Pavan. Sonker, Vandana. Patil, Manish. Agrawal, Ashish. Pathak Objective: To study the role of Vitamin B12 as an etiological factor in patients of infantile tremor [...]

Background/Objectives: In India, approx. 70% of the adolescent girls are anaemic (haemolgobin [less than] 120 g/l). The present study was a supervised randomised double-blind clinical trial conducted among adolescent girls (11-18 years) to assess and compare the impact of weekly iron folic acid (IFA) supplementation with or without vitamin B12 on reduction in the prevalence of anaemia and on blood/serum levels of haemoglobin, serum ferritin, folic acid and vitamin B12. Subjects/Methods: Community-based randomized controlled trial was carried out in Kirti Nagar slums of West Delhi. A total of 446 mild (100-119 g/l) and moderate (70-99 g/l) anaemic volunteer adolescent girls were identified and randomised into two groups. Weekly supervised supplementation was given for 26 weeks: Group A (n=222): iron (100 mg), folic acid (500 mcg) and placebo; Group B (n=224): iron (100 mg), folic acid (500 mcg) and cyanocobalamin (500 mcg for 6 weeks and 15 mcg for 20 weeks). Haemoglobin, serum ferritin, folic acid and vitamin B12 levels were assessed at baseline and after intervention. A total of 373 subjects completed 26 weeks of supplementation successfully. Results: The mean haemoglobin increased from 106.7[+ or -]11.2 g/l and 108.9[+ or -]8.91 g/l in Group A and Group B at baseline to 116.4[+ or -]10.8 g/l (P [less than] 0.001) and 116.5[+ or -]10.26 g/l (P [less than] 0.001) at post-intervention, respectively, with the reduction in the prevalence of anaemia by 35.9% in Group A and 39.7% in Group B (P [greater than] 0.05). A total of 63.3% participants had deficient vitamin B12 levels ( [less than] 203 pg/ml) at baseline, which reduced to 40.4% after intervention with cyanocobalamin, whereas no change was observed in vitamin B12 status in the other group. Significant reduction (P=0.01) in the prevalence of serum ferritin deficiency ( [less than] 15 ng/ml) was observed in the group supplemented with vitamin B12 (from 36.5 to 6.4%) as compared with the other group supplemented with only IFA (from 39.1 to 15.2%). Conclusions: IFA supplementation with or without vitamin B12 is an effective measure to cure anaemia. Although addition of vitamin B12 had similar impact on improving haemoglobin status as IFA alone, it resulted in better ferritin status. Hence, more multi-centre studies with a longer duration of supplementation or higher dose of vitamin B12 may be undertaken to assess the possible impact of vitamin B12 on improving haemoglobin levels in the population. European Journal of Clinical Nutrition (2016) 70, 730-737; doi: 10.1038/ejcn.2015.215; published online 23 December 2015, Author(s): P G Bansal [1]; G S Toteja [1]; N Bhatia [2]; N K Vikram [3]; A Siddhu [2] Introduction Iron deficiency anaemia is a major public health problem in [...]