The Continued Need for the Routine Assessment of Folate Status.

OBJECTIVE: The Choosing Wisely initiative recommended cessation of folate measurement, suggesting folate supplementation in macrocytic anemia. This study reviewed the need for continued blood folate testing at a large SafetyNet county teaching hospital. METHODS: Red blood cell (RBC) folate, vitamin B12, iron, ferritin, and hemoglobin results were obtained for utilization review. RESULTS: Of the 593 RBC folate results, 69 (11.7%) were deficient and 30 (5%) had high values. Collectively, 369 (73.9%) had normal vitamin B12 levels, 342 (70%) had low hemoglobin, 184 (62.5) had normal and 57 (19.4%) had low ferritin, 122 (38.2%) had normal and 188 (59%) had low iron levels. A total of 41 (12%) had normal folate, low ferritin, low hemoglobin, and low iron, suggestive of iron deficiency anemia. There were 11 patients who exhibited low folate, low or normal ferritin, low hemoglobin, and low iron levels, suggesting combined folate and iron deficiency anemias. CONCLUSION: This study highlights the need for institutions to assess the applicability of national recommendations to their local population.

Assessment of Vitamin B12 Deficiency and Risk Factors in Healthy Infants.

OBJECTIVE: To study vitamin B12 deficiency in apparently healthy infants and their mothers and assess the risk factors. METHODS: A hospital-based, cross-sectional, observational study was conducted from July 2016 through December 2017. Consecutive healthy and normally developing infants were enrolled. Red blood cell folate, plasma vitamin B12, homocysteine and methylmalonic acid levels of mothers and infants were assessed. RESULTS: Seventy-four healthy infants were enrolled. Male-to-female ratio was 1.5:1. Anemia in 66.2% (n = 49), low plasma B12 in 17.6% (n = 13), hyperhomocysteinemia in 48.6% (n = 36), plasma methylmalonic acid in 100% (n = 74) and 'confirmed' B12 deficiency in 38% (n = 28) infants were noted. The proportion of hyperhomocysteinemia increased to 75.7% (n = 56) infants using a lower cut-off of >10 µmol/L. In mothers, low B12 in 19%, hyperhomocysteinemia in 57% and elevated plasma methylmalonic acid in 100% were noted. Median plasma B12 level was 314 pg/ml (IQR 221-421), median plasma homocysteine 15.4 µmol/L (IQR 11.3-21.7) and median plasma methylmalonic acid was 8.28 µmol/L (IQR 4.4-13.1) in mothers. Folate deficiency was noted in 9.4% infants and 12% of mothers. Overall, 63.5% mothers were vegetarian and, 64% of the mothers of infants with confirmed vitamin B12 deficiency were pure vegetarians. Odds of developing vitamin B12 deficiency increased by more than 5 times in those whose mothers' serum vitamin B12 levels were low as compared to normal maternal vitamin B12 levels (OR 5.42; 95% CI: 1.96-16.6; p 0.002). CONCLUSIONS: There is a high prevalence of vitamin B12 deficiency in infants and their mothers. There is urgent need to supplement our population with vitamin B12.

Metformin Usage Index and assessment of vitamin B12 deficiency among metformin and non-metformin users with type 2 diabetes mellitus.

AIM: The present study aimed to evaluate the combined effect of both dose and duration of metformin therapy on vitamin B12 levels in patients with type 2 diabetes mellitus (T2D). METHODS: We recruited 2887 patients with T2D between January 2018 and November 2019 and categorized them into two groups (metformin and non-metformin users) matched for age, mean duration of diabetes, and BMI. We calculated the "Metformin Usage Index" (MUI) which was defined as the product of the dose of metformin (mg) used and its duration divided by 1000. Vitamin B12 levels were compared between the two groups, and its association with MUI was assessed using correlation and multistep logistic regression analyses. RESULTS: Vitamin B12 levels < 200 pg/ml and between 200 and 300 pg/ml were noted among 24.5% and 34.5% metformin users, respectively; this was significantly higher than among non-metformin users (17.3% and 22.6%, respectively) [P < 0.001]. Overall, a vitamin B12 level < 300 pg/ml was found in 52.2% of the subjects. There was a significant association between an MUI > 5 and a high risk of vitamin B12 deficiency [P < 0.01]. The highest risk was observed among patients with an MUI > 15 [odds ratio (OR) 6.74, 95% CI 4.39-10.4] followed by patients with an MUI > 10 (OR 5.12, 95% CI 3.12-8.38). CONCLUSIONS: The MUI can be employed as a risk assessment tool for evaluation of vitamin B12 deficiency in patients with T2D. Further prospective studies are required to determine the MUI thresholds in populations with good nutritional statuses and low prevalence of vitamin B12 deficiency.

Infant Serum and Maternal Milk Vitamin B-12 Are Positively Correlated in Kenyan Infant-Mother Dyads at 1-6 Months Postpartum, Irrespective of Infant Feeding Practice.

Background: Vitamin B-12 is an essential nutrient required for many functions including DNA synthesis, erythropoiesis, and brain development. If maternal milk vitamin B-12 concentrations are low, infants may face elevated risks of deficiency when exclusively breastfed. Objective: We evaluated cross-sectional associations between infant serum vitamin B-12 concentrations and maternal milk vitamin B-12 concentrations at 1-6 mo postpartum among an unsupplemented population in rural western Kenya, and assessed biological demographic, and dietary characteristics associated with adequate infant serum vitamin B-12. Methods: We modeled 1) infant serum vitamin B-12 using maternal milk vitamin B-12 concentration with linear regression; and 2) adequate (>220 pmol/L) infant serum vitamin B-12 using hypothesized biological, demographic, and dietary predictors with logistic regression. In both models, we used generalized estimating equations to account for correlated observations at the cluster-level. Results: The median (quartile 1, quartile 3) infant serum vitamin B-12 concentration was 276 pmol/L (193, 399 pmol/L) and approximately one-third of infants had serum vitamin B-12 ≤220 pmol/L, indicating that they were vitamin B-12 depleted or deficient. There was a positive correlation between maternal milk and infant serum vitamin B-12 (r = 0.36, P < 0.001) and in multivariable analyses, maternal milk vitamin B-12 concentration was significantly associated with infant serum vitamin B-12 adequacy (P-trend = 0.03). Conclusions: Despite a high prevalence (90%) of maternal milk vitamin B-12 concentrations below the level used to establish the Adequate Intake (<310 pmol/L), there was a low prevalence of infant vitamin B-12 deficiency. We found few factors that were associated with infant vitamin B-12 adequacy in this population, including infant feeding practices, although maternal vitamin B-12 status was not measured. The contribution of maternal milk to infant vitamin B-12 status remains important to quantify across populations, given that maternal milk vitamin B-12 concentration is modifiable with supplementation. This trial was registered at clinicaltrials.gov as NCT01704105.

Eggs early in complementary feeding increase choline pathway biomarkers and DHA: a randomized controlled trial in Ecuador.

Background: Choline status has been associated with stunting among young children. Findings from this study showed that an egg intervention improved linear growth by a length-for-age z score of 0.63.Objective: We aimed to test the efficacy of eggs introduced early in complementary feeding on plasma concentrations of biomarkers in choline pathways, vitamins B-12 and A, and essential fatty acids.Design: A randomized controlled trial, the Lulun ("egg" in Kichwa) Project, was conducted in a rural indigenous population of Ecuador. Infants aged 6-9 mo were randomly assigned to treatment (1 egg/d for 6 mo; n = 80) and control (no intervention; n = 83) groups. Socioeconomic data, anthropometric measures, and blood samples were collected at baseline and endline. Household visits were made weekly for morbidity surveillance. We tested vitamin B-12 plasma concentrations by using chemiluminescent competitive immunoassay and plasma concentrations of choline, betaine, dimethylglycine, retinol, essential fatty acids, methionine, dimethylamine (DMA), trimethylamine, and trimethylamine-N-oxide (TMAO) with the use of liquid chromatography-tandem mass spectrometry.Results: Socioeconomic factors and biomarker concentrations were comparable at baseline. Of infants, 11.4% were vitamin B-12 deficient and 31.7% marginally deficient at baseline. In adjusted generalized linear regression modeling, the egg intervention increased plasma concentrations compared with control by the following effect sizes: choline, 0.35 (95% CI: 0.12, 0.57); betaine, 0.29 (95% CI: 0.01, 0.58); methionine, 0.31 (95% CI: 0.03, 0.60); docosahexaenoic acid, 0.43 (95% CI: 0.13, 0.73); DMA, 0.37 (95% CI: 0.37, 0.69); and TMAO, 0.33 (95% CI: 0.08, 0.58). No significant group differences were found for vitamin B-12, retinol, linoleic acid (LA), α-linolenic acid (ALA), or ratios of betaine to choline and LA to ALA.Conclusion: The findings supported our hypothesis that early introduction of eggs significantly improved choline and other markers in its methyl group metabolism pathway. This trial was registered at clinicaltrials.gov as NCT02446873.

Vitamin B12 screening in metformin-treated diabetics in primary care: were elderly patients less likely to be tested?

Low serum B12 level is a common occurrence in patients with type 2 diabetes (T2DM) treated with metformin. There is lack of evidence concerning blood testing of vitamin B12 and current clinical guidelines make no recommendations on the detection or prevention of vitamin B-12 deficiency during metformin treatment. Our objective was to examine the current practice and clinical determinants of vitamin B12 testing in metformin treated T2DM patients. Data were collected from health maintenance organization patients, and consisted of T2DM patients who were newly prescribed metformin from 2008 to 2013. Patients were randomly divided into two subgroups: referred for a vitamin B12 blood test, and did not receive a referral. The demographic data and medical characteristics were analyzed. 5131 patients began taking metformin during the study period. Of these 2332 (44.5 %) had vitamin B12 tested. Significant differences were found between the groups in regard to glycosylated hemoglobin, low density lipoprotein, systolic blood pressure, dyslipidemia, chronic renal failure, and disease duration. A significant positive association (p < .05) was found between vitamin B12 testing and insulin treatment, retinopathy, neuropathy and hypertension. Vitamin B12 in elderly (>75 years) patients was significantly lower (p < .01). Insulin treatment, hypertension, and chronic diabetic complications in metformin treated T2DM patients are associated with higher rates of vitamin B12 testing. T2DM patients 75 years and above were less likely to be tested for B12 deficiency.

Comparative Assessment of Vitamin-B12, Folic Acid and Homocysteine Levels in Relation to p53 Expression in Megaloblastic Anemia.

BACKGROUND: Megaloblastic anemia (MBA), also known as macrocytic anemia, is a type of anemia characterized by decreased number of RBCs as well as the presence of unusually large, abnormal and poorly developed erythrocytes (megaloblasts), which fail to enter blood circulation due to their larger size. Lack of vitamin-B12 (VB12) and / or folate (Vitamin-B9, VB9) with elevated homocysteine is the key factor responsible for megaloblastic anemia. Prior studies have demonstrated the induction of apoptosis in these abnormal under-developed erythrocytes. However, it is not clear whether this apoptosis induction is due to elevated p53 level or due to any other mechanism. Furthermore, it is also not fully known whether decreased vitamin-B12 and / or folate are responsible for apoptosis induction mediated by p53 in pre-erythroblasts. METHODS: Levels of serum VB9, VB12 and homocysteine in 50 patients suffering from MBA were compared with 50 non-megaloblastic anemia control subjects, who were referred by the clinicians for bone marrow examination for medical conditions other than MBA. Next, we have measured the p53 expression in the paraffin embedded blocks prepared from bone marrow biopsy, using immunohistochemistry, and the expression levels correlated with VB9 and VB12 levels. RESULTS: Out of 50 MBA patients 40 (80%) and 44 (88%) subjects had very low VB12 and VB9 levels respectively. In contrast, only 2 (4%) and 12 (24%) non-megaloblastic anemia controls, out of 50 subjects, had low VB12 and VB9 respectively. Correlating with low vitamin B9 and B12, the homocysteine levels were high in 80% cases. But, only 20% non-megaloblastic controls exhibited high homocysteine in plasma. Immunohistochemical analysis for p53 expression showed a significantly high level of expression in MBA cases and no-or very low-expression in control subjects. Our correlation studies comparing the VB12 and VB9 levels with p53 expression concludes unusually high p53 levels in patients suffering from VB12 and VB9 deficiency induced MBA compared to control subjects not suffering from MBA. CONCLUSION: Tumor protein p53 is the key protein expressed heavily in the bone marrow biopsies of patients suffering from VB12 and VB9 deficiency induced MBA but not in control subjects. Hence, p53 expression could be used as a surrogate marker for confirming the VB9 and VB12 induced MBA.

Low serum levels of vitamin B12 in older adults with normal nutritional status by mini nutritional assessment.

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.

Vitamin B12 concentration and its association with sociodemographic factors in Colombian children: Findings from the 2010 National Nutrition Survey.

OBJECTIVE: Rapid changes in dietary patterns, economic development, and urbanization in low- to middle-income countries are fueling complex malnutrition states that need better characterization using population-level data. The aim of this study was to describe the key findings related to vitamin B12 status to identify the prevalence and associated sociodemographic factors in a representative sample of children in Colombia, based on the 2010 National Nutrition Survey. METHODS: We analyzed cross-sectional data from 6910 Colombian children between the ages of 5 and 12. Serum vitamin B12 concentrations were determined by chemiluminescence. Sociodemographic data was assessed by computer-assisted personal interview technology. RESULTS: Of the children assessed, 2.8% had vitamin B12 deficiency, defined as levels <200 pg/mL, and 18.1% had marginal vitamin B12 deficiency, defined as levels between 200 and 300 pg/mL. A multivariate logistic regression analysis revealed increased risks for vitamin B12 deficiency among children ages ≥9 y and for those living in the eastern, western, and southern regions of the country. No significant associations were found for ethnic groups, socioeconomic status, or urbanity levels. Being 11 y of age (odds ratio [OR], 2.16; 95% confidence interval [CI], 1.56-3.00; P = 0.0001), living in the west (Pacific) region of the country (OR, 3.92; 95% CI, 3.14-4.90; P = 0.0001), and being male (OR, 1.41; 95% CI, 1.20-1.65; P = 0.0001) were the factors most strongly associated with an increased risk for vitamin B12 deficiency. CONCLUSIONS: Compared with data from other Latin American countries, Colombian children have a lower prevalence of vitamin B12 deficiency; however the prevalence of marginal deficiency is substantial. Continued surveillance and implementation of interventions to improve dietary patterns among the high-risk groups identified should be considered.

Regional, Socioeconomic, and Dietary Risk Factors for Vitamin B-12 Deficiency Differ from Those for Folate Deficiency in Cameroonian Women and Children.

BACKGROUND: Representative data on folate and vitamin B-12 dietary intake and status in low-income countries are rare, despite the widespread adoption of folic acid fortification. OBJECTIVE: The purpose of this study was to evaluate folate and vitamin B-12 intake, status, and risk factors for deficiency before implementation of a national fortification program in Cameroon. METHODS: A nationally representative cross-sectional cluster survey was conducted in 3 ecologic zones of Cameroon (South, North, and the 2 largest cities, Yaoundé/Douala), and information on dietary intake was collected from 10 households in each of 30 randomly selected clusters per zone. In a subset of women and their 12- to 59-mo-old children (n = 396 pairs), plasma folate and vitamin B-12, as well as breast milk vitamin B-12, were analyzed. RESULTS: Vitamin B-12 and folate dietary intake patterns and plasma concentrations were similar for women and children. In the subsample, 18% and 29% of women and 8% and 30% of children were vitamin B-12 (≤ 221 pmol/L) and folate (< 10 nmol/L) deficient, respectively. Mean dietary folate ranged from 351 µg dietary folate equivalents/d in the North to 246 µg dietary folate equivalents/d in Yaoundé/Douala; plasma folate was negatively associated with socioeconomic status (P = 0.001). Plasma vitamin B-12 deficiency was similar in the South and North, 29% and 40%, respectively, but was only 11% in Yaoundé/Douala, and was positively associated with socioeconomic status. Mean breast milk vitamin B-12 was statistically significantly lower in the North (101 pmol/L) than in the South (296 pmol/L) or Yaoundé/Douala (349 pmol/L). CONCLUSIONS: Folate intake and status are inadequate among women and young children in Yaoundé/Douala, whereas low vitamin B-12 intake and status are more common in poor and rural areas, especially in the North. Different strategies may be needed to control deficiency of these nutrients in different regions of Cameroon.

Assessment of iron, folate and vitamin B12 status in severe acute malnutrition.

OBJECTIVES: To assess iron, folate and vitamin B12 status in hospitalized children aged between 6 mo to 5 y with severe acute malnutrition and its correlation with their clinico-epidemiological profile. METHODS: The study was conducted on 50 children with severe acute malnutrition. Anthropometric measurements were taken to determine their nutritional status. The demographic profile and relevant information of individual patient were collected by using structured proforma and an informed consent was taken for enrolling the children into the study. Serum ferritin, folate and vitamin B12 was estimated using electrochemiluminiscence (ECL) method. RESULTS: Seventy eight percent patients had weight/height (WT/HT) Z score < -3 standard deviation (3SD), 72 % with mid upper arm circumference (MUAC) <11.5 cm and 22 % of them had edematous malnutrition. Anemia was prevalent in 47(94 %) and there was significant correlation between WT/HT < -3SD and vitamin B 12 deficiency (p = 0.015). Significantly higher number of these patients had vitamin B12 deficiency as compared to folate and iron deficiency (p = 0.0006 each). CONCLUSIONS: Vitamin B12 deficiency was more common than iron and folate deficiencies in these patients with severe acute malnutrition.

Vitamin B12 serostatus in Colombian children and adult women: results from a nationally representative survey.

OBJECTIVE: Vitamin B12 deficiency is associated with many adverse health outcomes and is highly prevalent worldwide. The present study assesses the prevalence of vitamin B12 deficiency and marginal deficiency in Colombian children and women and examines the sociodemographic correlates of serum vitamin B12 concentrations in these groups. DESIGN: Cross-sectional, nationally representative survey. SETTING: Colombia. SUBJECTS: Children <18 years old (n 7243), pregnant women (n 1781), and non-pregnant women 18-49 years old (n 499). RESULTS: The overall prevalence of vitamin B12 deficiency (serum vitamin B12<148 pmol/l) and marginal deficiency (serum vitamin B12=148-221 pmol/l) was, respectively, 6.6 % (95 % CI 5.2%, 8.3%) and 22.5% (95% CI 21.1%, 23.9%). Pregnant women had the highest prevalence of deficiency (18.9 %; 95 % CI 16.6 %, 21.5 %) compared with non-pregnant adult women (18.5%; 95% CI 4.4%, 53.1%) and children (2.8 %; 95 % CI 2.3 % %, 3.3 %). In multivariable analyses among children, mean serum vitamin B12 was positively associated with female sex (12 pmol/l higher compared with males; P=0.004), secondary or higher education of the household head (12 pmol/l higher compared with primary or less; P=0.009) and food security (21 pmol/l higher compared with severe food insecurity; P=0.003). In multivariable analyses among pregnant women, mean serum vitamin B12 was positively associated with education of the household head and inversely associated with living in the National territories, Eastern or Pacific regions. CONCLUSIONS: The prevalence of vitamin B12 deficiency and marginal deficiency in Colombian women and children is substantial. The burden falls largely on adult women, those with lowest education and those living in the poorest, most rural regions of the country.

Vitamin B12 deficiency in inflammatory bowel disease: prevalence, risk factors, evaluation, and management.

BACKGROUND: Management of vitamin B(12) (cobalamin, Cbl) deficiency in inflammatory bowel disease (IBD) is often not evidenced-based because of uncertainty on whether it causes enough malabsorption to result in clinical disease. This systematic review examines whether IBD predisposes to Cbl deficiency. We provide an approach to the management of abnormal Cbl values in IBD based on current literature and consensus-based guidelines. METHODS: An extensive search of the Ovid MEDLINE and EMBASE databases by independent reviewers identified 42 articles with a total of 3732 patients evaluating Cbl deficiency in IBD. RESULTS: Crohn's disease without ileal resection, regardless of disease location in the ileum, did not increase the risk for Cbl deficiency. Ileal resections greater than 30 cm were associated with Cbl deficiency in Crohn's disease, whereas those less than 20 cm were not. The effects of 20 to 30 cm resections were inconsistent. Ulcerative colitis did not predispose to deficiency. All studies failed to use confirmatory biomarker testing as stipulated by diagnostic guidelines for Cbl deficiency. CONCLUSIONS: This literature does not support an association of Crohn's disease in general, regardless of ileal involvement, with Cbl deficiency. Only ileal resections greater than 20 cm in Crohn's disease predispose to deficiency and warrant treatment. Based on these findings, we suggest a diagnostic and therapeutic algorithm. All findings and recommendations require verification in further studies using confirmatory biomarkers as per diagnostic guidelines for Cbl deficiency. Serum Cbl levels alone are likely insufficient to diagnose deficiency in asymptomatic patients.

Proton pump inhibitor and histamine 2 receptor antagonist use and vitamin B12 deficiency.

IMPORTANCE: Proton pump inhibitors (PPIs) and histamine 2 receptor antagonists (H2RAs) suppress the production of gastric acid and thus may lead to malabsorption of vitamin B12. However, few data exist regarding the associations between long-term exposure to these medications and vitamin B12 deficiency in large population-based studies. OBJECTIVE: To study the association between use of PPIs and H2RAs and vitamin B12 deficiency in a community-based setting in the United States. DESIGN, SETTING, AND PATIENTS: We evaluated the association between vitamin B12 deficiency and prior use of acid-suppressing medication using a case-control study within the Kaiser Permanente Northern California population. We compared 25,956 patients having incident diagnoses of vitamin B12 deficiency between January 1997 and June 2011 with 184,199 patients without B12 deficiency. Exposures and outcomes were ascertained via electronic pharmacy, laboratory, and diagnostic databases. MAIN OUTCOMES AND MEASURES: Risk of vitamin B12 deficiency was estimated using odds ratios (ORs) from conditional logistic regression. RESULTS: Among patients with incident diagnoses of vitamin B12 deficiency, 3120 (12.0%) were dispensed a 2 or more years' supply of PPIs, 1087 (4.2%) were dispensed a 2 or more years' supply of H2RAs (without any PPI use), and 21,749 (83.8%) had not received prescriptions for either PPIs or H2RAs. Among patients without vitamin B12 deficiency, 13,210 (7.2%) were dispensed a 2 or more years' supply of PPIs, 5897 (3.2%) were dispensed a 2 or more years' supply of H2RAs (without any PPI use), and 165,092 (89.6%) had not received prescriptions for either PPIs or H2RAs. Both a 2 or more years' supply of PPIs (OR, 1.65 [95% CI, 1.58-1.73]) and a 2 or more years' supply of H2RAs (OR, 1.25 [95% CI, 1.17-1.34]) were associated with an increased risk for vitamin B12 deficiency. Doses more than 1.5 PPI pills/d were more strongly associated with vitamin B12 deficiency (OR, 1.95 [95% CI, 1.77-2.15]) than were doses less than 0.75 pills/d (OR, 1.63 [95% CI, 1.48-1.78]; P = .007 for interaction). CONCLUSIONS AND RELEVANCE: Previous and current gastric acid inhibitor use was significantly associated with the presence of vitamin B12 deficiency. These findings should be considered when balancing the risks and benefits of using these medications.

Effectiveness of the National Program of Complementary Feeding for older adults in Chile on vitamin B12 status in older adults; secondary outcome analysis from the CENEX Study (ISRCTN48153354).

BACKGROUND: Older people are at increased risk of vitamin B12 deficiency and the provision of fortified foods may be an effective way to ensure good vitamin B12 status in later life. AIM: To evaluate the effectiveness of a vitamin B12 fortified food provided by a national program of complementary food for older people on plasma vitamin B12 levels. SUBJECTS AND METHODS: A random sub-sample of 351 subjects aged 65-67 y from a large cluster randomised controlled trial provided blood samples at baseline and after 24 months of intervention. The intervention arm (10 clusters 186 participants) received a vitamin B12 fortified food designed to deliver 1.4 µg/day, while the control arm did not receive complementary food (10 clusters, 165 participants). Serum vitamin B12 and folate levels determined by radioimmunoassay were used to estimate the effect of intervention on vitamin B12 levels, adjusting for baseline levels and sex. RESULTS: Attrition at 24 months was 16.7% and 23.6% in the intervention and control arms respectively (p = 0.07). Over 24 months of intervention, mean (95% CI) serum vitamin B12 decreased from 392 (359-425) pmol/dL to 357 (300-414) pmol/dL (p < 0.07) in the intervention arm and from 395 (350-440) pmol/dL to 351 (308-395) pmol/dL in the control arm. There was no significant effect of the intervention on folate status. DISCUSSION: Our findings suggest that foods fortified with 1.4 µg/daily vitamin B12 as provided by Chile's national programme for older people are insufficient to ensure adequate vitamin B12 levels in this population. Chile has a long and successful experience with nutrition intervention programs; however, the country's changing demographic and nutritional profiles require a constant adjustment of the programs.

The cost-effectiveness of mandatory folic acid fortification in Australia.

The Australian government recently introduced mandatory folic acid fortification of bread to reduce the incidence of neural tube defects (NTDs). The economic evaluation of this policy contained a number of limitations. This study aimed to address the limitations and to reconsider the findings. Cost-effectiveness analysis was used to assess the cost and benefits of mandatory versus voluntary folic acid fortification. Outcomes measures were quality-adjusted life-years (QALYs), life-years gained (LYG), avoided NTD cases, and additional severe neuropathy cases. Costs considered included industry costs and regulatory costs to the government. It was estimated that mandatory fortification would prevent 31 NTDs, whereas an additional 14 cases of severe neuropathy would be incurred. Overall, 539 LYG and 503 QALYs would be gained per year of mandatory compared with voluntary fortification. Mandatory fortification was cost-effective at A$10,723 per LYG and at A$11,485 per QALY. Probabilistic sensitivity analysis showed that at A$60,000 and A$151,000 per QALY, the probability that mandatory fortification was the most cost-effective strategy was 79% and 85%, respectively. Threshold analysis of loss of consumer choice indicated that with a compensation value above A$1.21 [assuming a willingness to pay (WTP) threshold of A$60,000 per QALY] or A$3.19 (assuming a WTP threshold of A$151,000 per statistical life-year) per capita per year mandatory fortification would not be cost-effective. Mandatory fortification was found to be cost-effective; however, inclusion of the loss of consumer choice can change this result. Even with mandatory fortification, mean folate intake will remain below the recommended NTD preventive level.

Vitamin B12 and cognitive function: an evidence-based analysis.

BACKGROUND: More than 2.9 million serum vitamin B12 tests were performed in 2010 in Ontario at a cost of $40 million. Vitamin B12 deficiency has been associated with a few neurocognitive disorders. OBJECTIVE: To determine the clinical utility of B12 testing in patients with suspected dementia or cognitive decline. METHODS: Three questions were addressed: Is there an association between vitamin B12 deficiency and the onset of dementia or cognitive decline? Does treatment with vitamin B12 supplementation improve cognitive function in patients with dementia or cognitive decline and vitamin B12 deficiency? What is the effectiveness of oral versus parenteral vitamin B12 supplementation in those with confirmed vitamin B12 deficiency? A literature search was performed using MEDLINE, Embase, EBSCO Cumulative Index to Nursing & Allied Health Literature (CINAHL), the Cochrane Library, and the Centre for Reviews and Dissemination database, from January 2002 until August 2012. RESULTS: Eighteen studies (7 systematic reviews and 11 observational studies) were identified to address the question of the association between B12 and the onset of dementia. Four systematic reviews were identified to address the question of the treatment of B12 on cognitive function. Finally, 3 randomized controlled trials were identified that compared oral B12 to intramuscular B12. CONCLUSIONS: Based on very low quality evidence, there does appear to be an association between elevated plasma homocysteine levels (a by-product of B vitamins) and the onset of dementia. Based on moderate quality evidence, but with less than optimal duration of follow-up, treatment with B12 supplementation does not appreciably change cognitive function. Based on low to moderate quality of evidence, treatment with vitamin B12 and folate in patients with mild cognitive impairment seems to slow the rate of brain atrophy. Based on moderate quality evidence, oral vitamin B12 is as effective as parenteral vitamin B12 in patients with confirmed B12 deficiency. PLAIN LANGUAGE SUMMARY: Low levels of vitamin B12 have been associated with neurocognitive disorders. This evidence-based analysis assessed the usefulness of serum vitamin B12 testing as it relates to brain function. This review found very low quality evidence that suggests a connection between high plasma homocysteine levels (a by-product of B vitamin metabolism in the body) and the onset of dementia. Moderate quality of evidence indicates treatment with vitamin B12 does not improve brain function. Moderate quality of evidence also indicates treatment using oral vitamin B12 supplements is as effective as injections of vitamin B12.

Unmetabolized folic acid prevalence is widespread in the older Irish population despite the lack of a mandatory fortification program.

BACKGROUND: In 2006 the Food Safety Authority of Ireland recommended mandatory folic acid fortification of flour for the prevention of neural tube defects in addition to the existing extensive voluntary folic acid fortification culture in place there. This recommendation is now suspended until further scientific evidence surrounding safety becomes available. The safety issues include concerns about the masking of vitamin B-12 deficiency and potential cancer acceleration, both of which may be of concern for the elderly population. OBJECTIVE: The aim of this study was to measure the basal (fasted) concentrations of unmetabolized folic acid in the plasma of an elderly population group exposed to this liberal voluntary fortification of foodstuffs in Ireland. DESIGN: We invited participants aged 60-86 y from the Lifeways Cross-Generation Cohort Study to participate in this project. After providing informed consent, the participants were invited to provide fasting blood samples and to complete a standard food-frequency questionnaire and a questionnaire on recent and habitual intakes of folic acid. Samples were assayed for total plasma folate, red blood cell folate, homocysteine, and unmetabolized folic acid. RESULTS: A total of 137 subjects with a mean age of 67.4 y were studied. Unmetabolized folic acid was detected in 94.1% of the cohort with a mean concentration of 0.39 nmol/L (range: 0.07-1.59 nmol/L), accounting for 1.3% of total plasma folate. CONCLUSION: These results indicate unmetabolized folic acid in plasma in most of this elderly Irish cohort, even after an overnight fast. These results should be considered carefully by those legislating in this area.

Oral versus intramuscular administration of vitamin B12 for the treatment of patients with vitamin B12 deficiency: a pragmatic, randomised, multicentre, non-inferiority clinical trial undertaken in the primary healthcare setting (Project OB12).

BACKGROUND: The oral administration of vitamin B12 offers a potentially simpler and cheaper alternative to parenteral administration, but its effectiveness has not been definitively demonstrated. The following protocol was designed to compare the effectiveness of orally and intramuscularly administered vitamin B12 in the treatment of patients ≥65 years of age with vitamin B12 deficiency. METHODS/DESIGN: The proposed study involves a controlled, randomised, multicentre, parallel, non-inferiority clinical trial lasting one year, involving 23 primary healthcare centres in the Madrid region (Spain), and patients ≥65 years of age. The minimum number of patients required for the study was calculated as 320 (160 in each arm). Bearing in mind an estimated 8-10% prevalence of vitamin B12 deficiency among the population of this age group, an initial sample of 3556 patients will need to be recruited. Eligible patients will be randomly assigned to one of the two treatment arms. In the intramuscular treatment arm, vitamin B12 will be administered as follows: 1 mg on alternate days in weeks 1 and 2, 1 mg/week in weeks 3-8,and 1 mg/month in weeks 9-52. In the oral arm, the vitamin will be administered as: 1 mg/day in weeks 1-8 and 1 mg/week in weeks 9-52. The main outcome variable to be monitored in both treatment arms is the normalisation of the serum vitamin B12 concentration at weeks 8, 26 and 52; the secondary outcome variables include the serum concentration of vitamin B12 (in pg/ml), adherence to treatment, quality of life (EuroQoL-5D questionnaire), patient 3satisfaction and patient preferences. All statistical tests will be performed with intention to treat and per protocol. Logistic regression with random effects will be used to adjust for prognostic factors. Confounding factors or factors that might alter the effect recorded will be taken into account in analyses. DISCUSSION: The results of this study should help establish, taking quality of life into account, whether the oral administration of vitamin B12 is an effective alternative to its intramuscular administration. If this administration route is effective, it should provide a cheaper means of treating vitamin B12 deficiency while inducing fewer adverse effects. Having such an alternative would also allow patient preferences to be taken into consideration at the time of prescribing treatment. TRIAL REGISTRATION: This trial has been registered with ClinicalTrials.gov, number NCT 01476007, and under EUDRACT number 2010-024129-20.

The oldest old: red blood cell and plasma folate in African American and white octogenarians and centenarians in Georgia.

OBJECTIVE: To determine the overall folate status of a population-based multi-ethnic sample of octogenarians and centenarians and the specific dietary, demographic and physiological factors associated with observed abnormalities. DESIGN: Population-based multiethnic sample of adults aged 80 to 89 and 98 and above. SETTING: Northern Georgia, USA. PARTICIPANTS: Men and women aged 80 to 89 (octogenarians, n = 77) and 98 and older (centenarians, n = 199). ANALYSES: Wilcoxon rank sum tests, and Chi square and logistic regression analyses were used to examine associations of low and high folate status with hematological indicators and other variables of interest. RESULTS: The prevalence of low red blood cell (RBC) folate was low overall, but tended to be higher in centenarians than in octogenarians (6.5% vs. 1.3%, p = 0.058; defined as RBC folate < 317 nmol/L). The risk of having lower RBC folate (< 25th vs. > 25th percentile for RBC folate for 60yr+ in NHANES 1999-2000) was greater in association with vitamin B12 deficiency (OR = 5.36; 95%CI: 2.87-10.01), African American race (OR = 4.29; 95%CI: 2.08-8.83), and residence in a skilled nursing facility (OR = 3.25; 95%CI: 1.56-6.78) but was not influenced by age, gender, B-vitamin supplement use, high/low food score or presence of atrophic gastritis. Combined high plasma folate and low vitamin B12 status was present in some individuals (n=11), but was not associated with increased prevalence of anemia or cognitive impairment in this study. CONCLUSIONS: Low RBC folate status (< 317 nmol/L) was rare in this post folic acid fortification sample of octogenarians and centenarians. RBC folate status (< 25th percentile) was strongly associated with 1) vitamin B12 deficiency, which has strong implications for vitamin treatment, and 2) with being African American, suggesting racial disparities exist even in the oldest old.