Search

Vitamin B12 (B12) is a molecule involved in several biological. Abnormally high levels are frequently found, but their causes can be multiple, and consequences have not been clearly elucidated. The objective of this review was to summarize the current evidence on the associations of elevated B12 and the development of cancer, and all-cause mortality in adults. Six references looking at mortality and seven looking at cancer risk were included. The evidence suggests an association between elevated B12 with a higher risk of cancer, with risk ratios ranging 1,88 to 5,9. There was less consistent evidence linking vitamin B12 and mortality. Elevated B12 levels exceeding 1000 pg/L, if sustained and unexplainable, warrant a comprehensive individual assessment of each patient. This evaluation should encompass various potential factors contributing to the elevation, aiming to effectively guide the diagnostic process of neoplastic diseases. Clinical longitudinal observational studies have suggested a potential link between heightened B12 levels and the risks of cancer and mortality. Nonetheless, these studies have been retrospective cohort studies, and lack a defined threshold point of B12 levels. Studies have documented a positive correlation between elevated levels of B12 and the incidence of lung, pancreatic, and liver cancers, as well as certain hematological neoplasms, particularly those related to the myeloid lineage. Conversely, a consistent negative association has been observed in the context of breast cancer. Findings concerning neoplasms of the lower gastrointestinal tract and prostate display contradictory outcomes. The diagnostic significance of elevated B12 levels among patients already diagnosed with cancer remains uncertain and could potentially be linked to reverse causality. [ABSTRACT FROM AUTHOR]

Plant-based diets are increasingly popular worldwide. A well-planned plant-based diet lowers the risk of cardiovascular disease, type 2 diabetes and certain cancers. In contrast, a poorly planned plant-based diet increases the risk of certain micronutrient deficiencies, chiefly, vitamin B12 (B12). Because B12 is not present in plants or in unfortified plant-based foodstuffs, the safest way to prevent its deficiency in plant-based diets is to take an oral B12 supplement. Studies determining the dose and frequency of B12 to be taken by healthy individuals on a plant-based diet to support an adequate B12 status are scarce. Here, we summarize the natural sources, metabolic requirements, biomarker findings with and without supplementation with B12, and current recommendations to help prevent vitamin B12 deficiency in healthy individuals adhering or transitioning to plant-based diets. This review focuses on the prevention of vitamin B12 deficiency in healthy individuals adhering to plant-based diets. The information covered in this review does not apply to individuals suffering from autoimmune-based malabsorption of vitamin B12 resulting from pernicious anemia due to atrophic gastritis, other acquired causes of B12 malabsorption or to those with genetic disorders that impair vitamin B12 absorption, transport and utilization. Plain language title: Vitamin B12 in Plant-Based Diets Plain language summary: Plant-based diets are increasingly popular worldwide. Because vitamin B12 is not found in plants, individuals must acquire the micronutrient by consuming fortified foods or by taking an oral vitamin B12 supplement. We review B12 sources, required daily intake, and use of B12 supplements among those on plant-based diets. The safest way to prevent B12 deficiency in individuals adhering to plant-based diets is by using an oral B12 supplement. [ABSTRACT FROM AUTHOR]

Obesity, whose prevalence is increasing globally, is malnutrition that causes micro/macronutrients and vitamin deficiencies in adolescents. Vitamin B12 plays a prominent role in the body systems such as remethylation, deoxidation, and DNA synthesis. We aimed to examine the relationship between severe obese/obese adolescents and vitamin B12 levels in this study. This study was conducted as a case–control study consisting of 44 obese and 40 healthy control adolescents aged 11–17 years. Obesity was diagnosed using body mass index (BMI) charts defined by the World Health Organization according to age and gender. Vitamin B12 deficiency was found to be 34.1% in the patient obesity group, while it was 12.5% in the control group (p = 0.02). Homeostatic Model Assessment for Insulin Resistance levels were found to be 3.09 (1.9–5.29) higher in the severely obese group (p < 0.001). The median level of vitamin B12 in the obese group was 173 (122.5–220.7) in the severe obese group, 197 (146.5–302.7) in the obese group, and 252.5 (192.8–302) in the control group (p = 0.021). We found that obesity has a 1.6-fold decreasing effect on vitamin B12 levels. This study shows the clinician the importance of monitoring BMI and vitamin B12 levels in obese adolescents, given the effects of vitamin B12 on neuronal migration, metabolic reactions, and many systems in the body. Further researches are needed to investigate the pathophysiology and effect of low vitamin B12 levels in obese adolescents. [ABSTRACT FROM AUTHOR]

Over the last decades, low vitamin B12 status has been reported in individuals with type 2 diabetes mellitus (T2DM). Metformin, the first-line therapy for lowering blood glucose, is the main driving factor behind this association. Although the relationship between vitamin B12 deficiency and metformin is well established, results of studies on the exact effect of the dose and duration of the therapy remain inconsistent. Additionally, a lack of consensus on the definition of vitamin B12 deficiency adds to the conflicting literature. The objectives of this review were to analyze and synthesize the findings on the effects of metformin dose and duration on vitamin B12 status in patients with T2DM and to outline the potential mechanisms underlying metformin's effect on vitamin B12. Metformin therapy has adversely affected serum vitamin B12 concentrations, a marker of vitamin B12 status. The metformin usage index (a composite score of metformin dose and duration) might serve as a potential risk assessment tool for vitamin B12 screening in patients with T2DM. Considering the health implications of suboptimal vitamin B12 status, vitamin B12 concentrations should be monitored periodically in high-risk patients, such as vegans who are receiving metformin therapy for T2DM. Additionally, it is prudent to implement lifestyle strategies concurrent with metformin therapy in individuals with T2DM, promoting an overall synergistic effect on their glycemic control. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to explore the association between N-6 adenine-specific DNA methyltransferase 1 (N6AMT1) single nucleotide polymorphisms (SNPs) and gestational diabetes mellitus (GDM) and the modification of the relationship by folate and vitamin B12. Methods: A cross-sectional study involving 1303 pregnant women (262 GDM and 1041 non-GDM) was performed in Tianjin, China. Nine SNPs in N6AMT1 were genotyped, and serum folate, vitamin B12, and homocysteine (Hcy) levels were measured. The logistic regression models determined the odds ratios (ORs) for SNPs in N6AMT1 and the gene-nutrition interactions on GDM. Results: N6AMT1 rs7282280, rs1048546, and rs1997605 were related to GDM under the dominant model after adjusting for multiple covariates. Individuals carrying the N6AMT1 rs7282280 TC/TT genotypes had a lower risk of developing GDM, regardless of serum folate and vitamin B12 levels. However, rs1048546 TG/GG genotypes were associated with lower GDM risk when serum folate ≥ 6.0 ng/mL. Pregnancies with the risk genotypes in N6AMT1 and higher serum folate or lower vitamin B12 are more prone to GDM. The study also showed a statistically significant additive interaction between N6AMT1 rs1997605 GG genotypes and lower vitamin B12 (RERI: 2.54; 95% CI: 0.17, 4.92). Conclusion: SNPs in N6AMT1 were found to be associated with GDM, and serum folate and vitamin B12 levels can modify their associations. [ABSTRACT FROM AUTHOR]

This article is a commentary on the role of vitamin B12 in age-related cognitive decline, with a meta-commentary on the misuse of the term "Alzheimer's Disease." The article describes the historical origins of the term "Alzheimer's Disease" and argues that the term should be restricted to a narrower segment of the age-related dementia spectrum. The article also outlines the role of vitamin B12 in age-related cognitive decline and outlines the rationale for the treatment of B12 deficiency to address a potentially reversible factor in cognitive decline. [ABSTRACT FROM AUTHOR]

Background: Nutritional anemia is a significant public health concern worldwide, particularly affecting young adults and children in Saudi Arabia, where inadequate nutrition is considered a primary contributing factor. This study aims to (i) examine the levels of serum iron, folate, and vitamin B12 in young adult students, with a focus on identifying any deficiencies and their association with anemia; (ii) explore the prevalence of mixed-deficiency anemia resulting from deficiencies in serum iron, folate, and vitamin B12 (iii) explore how sociodemographic characteristics and dietary habits influence serum iron, folate, and vitamin B12 levels. Materials and Methods: This cross-sectional study encompassed 158 young adult students at Jazan University, Saudi Arabia. Blood samples were collected following a comprehensive questionnaire addressing sociodemographic and health characteristics. These samples were analyzed for complete blood count, serum iron, folate, and vitamin B12 levels. Results: The findings of this study revealed a significant decrease in serum iron levels, with 70.6% of males and 88% in females exhibiting reduced level. Additionally, low levels of folate were observed in 4% of the study population, while deficiency in vitamin B12 was found in 2.2% of the study population. However, the simultaneous presence of low serum iron levels along with deficiencies in folate or vitamin B12 was not observed in the study participants. Conclusion: The study indicates that there is a high incidence of low serum iron and ferritin levels among university students in Saudi Arabia, which poses a considerable public health concern. Conversely, the prevalence of folate and vitamin B12 deficiencies among the students was comparatively low, and notably, there were no cases where these deficiencies were observed alongside iron deficiency. [ABSTRACT FROM AUTHOR]

Background: Diarrhoea is defined as stool frequency of more than three times in twenty-four hours or a stool weight of more than two hundred grams and it is labelled as chronic diarrhoea if it persists for more than four weeks. Chronic diarrhoea is a common gastrointestinal problem worldwide that affects three to fifteen percent of population. Objective was to determine the efficacy of vitamin B 12 replacement in treatment of chronic diarrhoea in vitamin B deficient patients. It was a Quasiexperimental study carried out at Pakistan Ordinance Factory (POF) Hospital Wah Cantt, from September 2023 to February 2024. Methods: All the new patients of chronic diarrhoea of ages between 12-65 years who had low serum vitamin B 12 and normal serum folate levels were included in the study. The patients were booked from Medicine and Allied outpatient and they were given parenteral vitamin B12. The sub-set of patients in whom diarrhoea was settled was followed up till six months. The efficacy was defined as settlement of diarrhoea with parenteral vitamin B12 within one week. The secondary outcomes were adequacy of serum vitamin B12 levels at 2 weeks, three months and six months after treatment. All patients (100%) had adequate B12 levels till follow up. Data was analyzed through SPSS. Results: Efficacy of parenteral B12 supplementation was seen in 16 (76.2%) patients. Out of sixteen patients who responded to vitamin B12 supplementation, 10 (47.6%) patients showed improvement in less than two days, 5 (23.8%) showed improvement in less than four days and 1 (4.8) patient stopped experiencing diarrhoea within seven days of intramuscular vitamin B12 with p-value of <0.001. Conclusion: Replacement of vitamin B 12 in patients with chronic diarrhoea having low vitamin B 12 results in settlement of diarrhoea. [ABSTRACT FROM AUTHOR]

Background and Objectives: Cobalamin, also known as vitamin B12, is essential for DNA synthesis and neurological functioning. Deficiency results in hematological and neurocognitive manifestations. One risk factor for vitamin B12 deficiency is the use of metformin, a common oral hypoglycemic agent. This study was conducted to determine cobalamin status in patients with type 2 diabetes mellitus at primary health care centers in Bahrain. Methods: This cross-sectional study was conducted in five randomly selected health centers in Bahrain. Vitamin B12 levels below 148 pmol/L were categorized as deficient, levels ranging from 148 to 221 pmol/L were considered borderline, and levels exceeding 221 pmol/L were classified as normal. Results: A total of 691 participants were included in the study, with a mean age of 58.7 years. The most common comorbid condition among our cohort was hypertension (63.1%), followed by dyslipidemia (53.1%). Analysis of the glycemic control showed that only 40% of the participants achieved control targets. Nearly 10% (9.4%, n=65) of the cohort had low levels of vitamin B12, and 31% had borderline values. A significant association was seen between low vitamin B12 levels and Bahraini nationality (p<0.001), and patients who engaged in weekly exercise (P=0.007). Furthermore, the analysis revealed that the use of metformin (P=0.037) and alcohol (P=0.012) was significantly associated with low levels of vitamin B12. Conclusion: Although the overall prevalence of B12 deficiency among patients with type 2 diabetes in Bahrain was low, patients at high risk of B12 deficiency, including metformin users and alcohol consumers, should be periodically screened to prevent the associated neurological and hematological sequela. [ABSTRACT FROM AUTHOR]

Background: preeclampsia is a common obstetric disorder that remains a leading cause of maternal and perinatal mortality and morbidity. Maternal serum concentrations of adiponectin, folate, homocysteine, and vitamin B12 have been found to be associated with pre-eclampsia. Nevertheless, reported studies involved still not clear with variable reliably. The aim of the present study is to examine the relationship between these biomarkers and pre-eclampsia and its severity in Iraqi population. Aims: The study aims to evaluate the association between maternal serum adiponectin, homocysteine, B12 and Folic acid and preeclampsia and its severity. Study design and setting. A case control study carried out in Al-Zahraa Maternity and Pediatric Teaching Hospital in Najaf city/ Iraq from the 1st of December 2019 to the 1st of December 2020. Patient and Methods: The study included 50 pregnant women with preeclampsia and a comparative control group of 50 normotensive pregnant women. Preeclamptic women were further subdivided into 14 women with severe preeclampsia and 36 women with mild preeclampsia. Serum Adiponectin, Homocysteine, B 12, and Folic acid were measured by using special ELIZA (Enzyme linked immunosorbent assay) technique. Results: There was a significant increment in the level of Adiponectin and Homocysteine while vitamin B12 and Folic acid were significantly decreased in preeclamptic pregnant women in comparison to the control group. On the other hand, there was no significant relation between the severity of preeclampsia and the level of Adiponectin, Homocysteine, Vitamin B 12, and Folic acid. Conclusion: Women with preeclampsia had significantly lower vitamin B12 and folic acid and significantly higher concentrations of adiponectin and homocysteine than normotensive pregnant women, but no relation with its severity. [ABSTRACT FROM AUTHOR]

Background and Objectives: Postoperative anemia remains a critical concern due to its association with adverse surgical outcomes. To address this issue, our study aimed to investigate the efficacy of intravenous iron therapy in promptly correcting anemia following surgery. Materials and Methods: Our study involved the prospective enrollment of patients undergoing elective orthopedic and general surgery, who were then randomized into two distinct groups: the Control group receiving placebo, and the Iron Group receiving intravenous iron therapy. Blood tests were conducted preoperatively as baseline measurements and on several postoperative days (PODs) - specifically PODs 1, 3, and 7. Results: Throughout the postoperative period, both groups exhibited significantly lower hemoglobin (Hb) concentrations compared to their respective baselines, with no statistically significant differences in postoperative Hb levels observed between the groups. Moreover, both groups demonstrated elevated serum erythropoietin, ferritin, and vitamin B12 levels, along with an increased reticulocyte count surpassing normal ranges. A considerable decline in serum iron levels was observed in both groups postoperatively. No substantial inter-group variances in hepcidin levels were identified. Conclusion: Our study indicated an absence of significant efficacy in correcting postoperative anemia among orthopedic and surgery patients, despite inducing higher reticulocyte counts within the initial week following the surgical procedure. Also, we discourage the practice of Vitamin B12 administration during the early postoperative period. [ABSTRACT FROM AUTHOR]

Purpose: There remains a data gap on vitamin B12 and folate level in maternal and child populations. This study aimed to assess the status of vitamin B12 and folate in maternal serum (MS) and umbilical cord serum (UCS).Materials and Methods: This was a planned secondary analysis of a case-control study. A total of 858 pregnant women during late pregnancy and their newborns in the hospitals of China were included. Maternal peripheral venous blood and neonatal umbilical cord blood were collected to determine serum vitamin B12 and folate concentration. Relationship of vitamin B12 or folate concentration between MS and UCS was assessed by a quantile regression model and the non-linear relationship between them was examined.Results: Nutritional status of serum folate was better than that of vitamin B12. Prevalence of deficiency in MS vitamin B12 and folate was 73.4% and 14.2%, respectively and these figures were about 17.8% and 0.1% in UCS. Both vitamin B12 and folate levels in UCS were significantly higher than those in MS (vitamin B12: 321.0 pg/mL vs 158.3 pg/mL, folate: 16.5 ng/mL vs 7.0 ng/mL, P < 0.001). The median UCS-MS ratio of vitamin B12 and folate was 2.0 (95% CI: 1.94– 2.06) and 2.4 (95% CI: 2.30– 2.53), respectively. The levels of folate and vitamin B12 in UCS increased nonlinearly with their increase in MS which presented an inverted U-shaped curve.Conclusion: Deficiency in vitamin B12 and folate in the women during late pregnancy in China is prevalent. Nutritional status of the two vitamins in umbilical cord serum is correlated nonlinearly with that in maternal serum. Folic acid supplementation may be accompanied with vitamin B12 to improve status of vitamin B12 and folate during pregnancy. [ABSTRACT FROM AUTHOR]

This was a longitudinal study utilising the Irish Longitudinal Study on Ageing (n 3849 aged ≥ 50 years) and investigated the relationship between blood plasma folate and B12 levels at baseline (wave 1) and incident depressive symptoms at 2 and 4 years (waves 2 and 3). A score ≥ 9 on the Center for Epidemiological Studies Depression Scale-8 at wave 2 or 3 was indicative of incident depressive symptoms. B12 status profiles (pmol/l) were defined as < 185, deficient low; 185 to < 258, low normal; > 258–601, normal and > 601 high. Folate status profiles (nmol/l) were defined as ≤ 10·0, deficient low; > 10–23·0, low normal; > 23·0–45·0, normal; >45·0, high. Logistic regression models were used to analyse the longitudinal associations. Both B12 and folate plasma concentrations were lower in the group with incident depressive symptoms v. non-depressed (folate: 21·4 v. 25·1 nmol/l; P = 0·0003; B12:315·7 v. 335·9 pmol/l; P = 0·0148). Regression models demonstrated that participants with deficient-low B12 status at baseline had a significantly higher likelihood of incident depression 4 years later (OR 1·51, 95 % CI 1·01, 2·27, P = 0·043). This finding remained robust after controlling for relevant covariates. No associations of folate status with incident depression were observed. Older adults with deficient-low B12 status had a 51 % increased likelihood of developing depressive symptoms over 4 years. The findings highlight the need to further explore the low-cost benefits of optimising vitamin B12 status for depression in older adults. [ABSTRACT FROM AUTHOR]

The fast spread of the coronavirus disease 2019 (COVID-19) epidemic and its high mortality were quickly noticed by the health community. B vitamins are essential micronutrients for the body with antioxidant, anti-inflammatory and immune-regulating properties. The present study can provide a comprehensive picture of the associations between B vitamins and COVID-19 incidence. This study was undertaken on 9189 adult participants of the Yazd Health Study (YaHS) and Taghzieh Mardom-e-Yazd (TAMIZ) study aged 20 to 69 years. Data on dietary intakes were obtained using a validated FFQ. Multivariable logistic regression analysis was used to evaluate the association between B vitamins and COVID-19. Our findings indicated that participants in the fourth quartile of vitamin B5 intake compared with the first quartile had a protective effect against COVID-19 (OR: 0·53, 95 % CI 0·28, 0·99, P -trend = 0·02) after adjustment for all possible confounds in model 3. In addition, participants in the third quartile of vitamin B12 intake compared with the first quartile (OR: 0·63, 95 % CI 0·40, 0·98, P -trend = 0·11) had fewer odds of COVID-19 after full adjustments for confounders. Our findings indicated no significant relationship between dietary intake of vitamin B1, B2, B3, B9 and B-complex and COVID-19. A higher intake of vitamin B5 could reduce the odds of COVID-19 by 47 %, and a moderate intake of vitamin B12 had a protective effect on COVID-19. Although our study has promising results, stronger clinical studies are needed. [ABSTRACT FROM AUTHOR]

Background: Recently, the role of biochemical factors in the etiology of oral squamous cell carcinoma (OSCC) has attracted some attention. Serum levels of biochemical factors may change in cancer patients. This study aimed to assess the serum level of folate, Vitamin B12, homocysteine, iron, copper, and selenium in patients with OSCC. Materials and Methods: This descriptive analytical study was conducted on 30 primary OSCC patients (15 males and 15 females) presenting to Imam Khomeini Cancer Institute, who had not yet undergone treatment. Blood samples were taken and serum levels of folate, Vitamin B12, homocysteine, iron, copper, and selenium were measured. Serum levels of micronutrients in patients with different tumor sizes were analyzed by one-way ANOVA. Serum levels of micronutrients were compared among groups with and without metastasis and lymph node involvement using Student's t-test (P < 0.05). Results: Serum levels of B12, folic acid, homocysteine, copper, iron, and selenium were 232.5 ± 102.68, 8.66 ± 4.06, 18.87 ± 8.81, 96.0 ± 22.64, 55.27 ± 40.58, and 92.47 ± 18.83 ng/mL, respectively. Relatively similar values were measured in patients with different tumor sizes with and without lymph node involvement and presence or absence distant metastasis. However, the serum level of folic acid in OSCC patients without lymph node involvement was significantly higher than that in OSCC patients with lymph node involvement (P < 0.05). Conclusion: Despite some variations, serum levels of micronutrients in OSCC patients were within the normal limits. Considering the variations in serum level of copper in OSCC patients, it may be used as a diagnostic marker. However, further studies are warranted in this respect. [ABSTRACT FROM AUTHOR]

Plant-based diets may increase the risk of vitamin B12 deficiency due to limited intake of animal-source foods, while dietary folate increases when adhering to plant-based diets. In this cross-sectional study, we evaluated the B12 and folate status of Norwegian vegans and vegetarians using dietary B12 intake, B12 and folic acid supplement use, and biomarkers (serum B12 (B12), plasma total homocysteine (tHcy), plasma methylmalonic acid (MMA) and serum folate). Vegans (n 115) and vegetarians (n 90) completed a 24-h dietary recall and a FFQ and provided a non-fasting blood sample. cB12, a combined indicator for evaluation of B12 status, was calculated. B12 status was adequate in both vegans and vegetarians according to the cB12 indicator; however 4 % had elevated B12. Serum B12, tHcy, MMA concentrations and the cB12 indicator (overall median: 357 pmol/l, 9·0 µmol/l, 0·18 µmol/l, 1·30 (cB12)) did not differ between vegans and vegetarians, unlike for folate (vegans: 25·8 nmol/l, vegetarians: 21·6 nmol/l, P = 0·027). Serum B12 concentration < 221 pmol/l was found in 14 % of all participants. Vegetarians revealed the highest proportion of participants below the recommended daily intake of 2 µg/d including supplements (40 v. 18 %, P < 0·001). Predictors of higher serum B12 concentrations were average daily supplement use and older age. Folate deficiency (< 10 nmol/l) was uncommon overall (< 2·5 %). The combined indicator cB12 suggested that none of the participants was B12-depleted; however, low serum B12 concentration was found in 14 % of the participants. Folate concentrations were adequate, indicating adequate folate intake in Norwegian vegans and vegetarians. [ABSTRACT FROM AUTHOR]

Hippocampus cells, responsible for learning and memory, are disturbed in Alzheimer's disease (AD), resulting in production of several inflammatory markers, such as neurexin 1 –neuroligin, cyclooxygenase–2 (COX–2), and caspase–3 proteins, used in measurement of AD's severity and development. Vitamin B12, which plays a role in brain functioning, has anti–inflammatory properties and its impairment is associated with apoptosis in Alzheimer's disease. This study aimed to investigate the effect of vitamin B12 on restoration of Synaptic Plasticity on scopolamine–induced AD in rats. To simulate AD, Rats, except the control group were i.p. injected with 3 mg/kg scopolamine. Before scopolamine the pretreatment group vitamin B12 (0.5, 2, and 4 mg/kg) was injected every day for the next 14 days. After 24 h, sectioning the rats' brains, the concentration of postsynaptic density protein 95 (PSD–95), neurexin 1–neurolgin, COX–2, and caspase–3 proteins in hippocampus were measured using immunoblotting. B12 significantly enhanced molecular balance. PSD–95 and neurexin 1 and neuroligin concentrations were significantly reduced, whereas COX–2 and activated caspase–3 were enhanced in the hippocampus of scopolamine–injected subjects. Their alterations were decreased after B12 administration. Vitamin B12 protected scopolamine–injected rats and inhibited hippocampal inflammation and apoptosis and preserved pre– and post–synaptic proteins and possibly synaptic integrity in hippocampus route. [ABSTRACT FROM AUTHOR]

Objective: To investigate the association between folate levels and the risk of gestational diabetes mellitus (GDM) risk during the whole pregnancy. Design: In this retrospective cohort study of pregnant women, serum folate levels were measured before 24 gestational weeks (GW). GDM was diagnosed between 24th and 28th GW based on the criteria of the International Association of Diabetes and Pregnancy Study Groups. General linear models were performed to examine the association of serum folate with plasma glucose (i.e. linear regressions) and risk of GDM (i.e. log-binomial regressions) after controlling for confounders. Restricted cubic spline regression was conducted to test the dosage–response relationship between serum folate and the risk of GDM. Setting: A sigle, urban hospital in Shanghai, China. Participants: A total of 42 478 women who received antenatal care from April 2013 to March 2017 were included. Results: Consistent positive associations were observed between serum folate and plasma glucose levels (fasting, 1-h, 2-h). The adjusted relative risks (RR) and 95 % CI of GDM across serum folate quartiles were 1·00 (reference), 1·15 (95 % CI (1·04, 1·26)), 1·40 (95 % CI (1·27, 1·54)) and 1·54 (95 % CI (1·40, 1·69)), respectively (P -for-trend < 0·001). The positive association between serum folate and GDM remained when stratified by vitamin B12 (adequate v. deficient groups) and the GW of serum folate measurement (≤13 GW v. >13 GWs) Conclusions: The findings of this study may provide important evidence for the public health and clinical guidelines of pregnancy folate supplementation in terms of GDM prevention. [ABSTRACT FROM AUTHOR]

The relationship between vitamin B12 and gestational diabetes mellitus (GDM) remains controversial. To comprehensively evaluate the relationship between vitamin B12 and GDM, and to provide more information on GDM prevention, this study provides a systematic review and meta-analysis of vitamin B12 and GDM. As of September 22, 2021, 304 articles were searched in PubMed, Web of Science, EMBASE, and Cochrane databases, of which 15 studies met the inclusion criteria. Results presented there was no association between maternal vitamin B12 concentration during the first trimester with GDM, however, low vitamin B12 concentration in the second or third trimester of pregnancy was related to an increased risk of GDM. Compared with the non-GDM group, the vitamin B12 concentration in the GDM group was remarkably decreased (MD: –10·79; 95%CI: –21·37, –0·21), and vitamin B12 deficiency increased the risk for GDM (OR: 1·59; 95%CI: 1·10, 2·29). These effects were more significant among Asians. In addition, an increased ratio of high folate to low vitamin B12 in serum also increased the risk of GDM (OR: 1·87; 95% CI: 1·46, 2·41). These results suggest that more vitamin B12 may need to be provided during pregnancy. [ABSTRACT FROM AUTHOR]

Folate and vitamin B12 are essential for growth. Our objective was to estimate their long-term effects on linear growth in North Indian children. This is a follow-up study of a factorial designed, double-blind, randomised, placebo-controlled trial in 1000 young children. Starting at 6–30 months of age, we gave folic acid (approximately 2 RDA), vitamin B12 (approximately 2 RDA), both vitamins or a placebo daily for 6 months. Six years after the end of supplementation, we measured height in 791 children. We used the plasma concentrations of cobalamin, folate and total homocysteine to estimate vitamin status. The effect of the interventions, the association between height-for-age z-scores (HAZ) and baseline vitamin status, and the interactions between supplementation and baseline status were estimated in multiple regression models. Mean (sd) age at follow-up was 7·4 (0·7) years (range 6 to 9 years). There was a small, non-significant effect of vitamin B12 on linear growth and no effect of folic acid. We observed a subgroup effect of vitamin B12 supplementation in those with plasma cobalamin concentration < 200 pmol/l (P for interaction = 0·01). The effect of vitamin B12 supplementation in this group was 0·34 HAZ (95 % CI 0·11, 0·58). We found an association between cobalamin status and HAZ in children not given vitamin B12 (P for interaction = 0·001). In this group, each doubling of the cobalamin concentration was associated with 0·26 (95 % CI 0·15, 0·38) higher HAZ. Suboptimal vitamin B12 status in early childhood seemingly limits linear growth in North Indian children. [ABSTRACT FROM AUTHOR]

Immune methods are measurement systems that can be affected by interference. The interfering substance may be endogenous immunoglobulins, antibodies, analyte-antibody complexes, and heterophile antibodies. In our study, we aimed to investigate the effect of macrovitamin B12 on high vitamin B12 levels measured using immune methods. Among the serum samples studied in our laboratory; serum from 145 individuals was determined as the patient group and serum from 50 individuals was determined as the control group. We investigated the effect of macroprotein on B12 measurement by using polyethylene glycol (PEG) precipitation, heterophile antibody blocking tube (HBT) and serial dilution methods. According to the recovery evaluation and the modified reference range evaluation after precipitation with PEG, the macrovitamin B12 percentage in the patient group was 58 (40%) and 65 (44.8%), respectively. There was no decrease in vitamin B12 values after the study with HBT. A lack of linearity was observed in 23 (18.7%) of 123 sera with serial dilution method. Macrovitamin B12 should be considered as a differential diagnosis of unexpectedly high vitamin B12 levels. According to the results of our study, we think that it would be appropriate to precipitate with PEG first when there is a suspicion of macrovitamin B12. In collaboration with clinical and laboratory, we recommend that the patient's clinical status and additional laboratory findings be examined, and the patient's sample should be evaluated and interpreted by a specialist in biochemistry by selecting the appropriate interference detection method. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to investigate the relationships of serum folate (vitamin B9), cobalamin (vitamin B12) levels and diet with semen parameters (semen standard parameters [SSP] and DNA fragmentation index [DFI]) in infertile men. Methods: Sperm samples were assessed for SSP and DFI (using the sperm chromatin dispersion test). Serum vitamin concentrations were measured with an immuno-electrochemiluminescence assay, and men completed a semi-quantitative food frequency questionnaire (FFQ). Results: Serum folate levels were positively correlated with sperm progressive motility and DFI. A comparison of SSP between two groups of patients according to serum folate concentration (B9 <4.840 ng/mL and B9 =4.840 ng/mL) showed significantly higher sperm concentration and sperm progressive motility in the latter group. However, there was no difference between these groups regarding DFI. Interestingly, serum folate levels were significantly higher in patients with a high DFI (using the cut-offs of 30% or 18%). FFQ data showed that the consumption of fruits and egg yolk correlated positively with sperm concentration and sperm motility, respectively. Conclusion: Serum folate levels showed significant associations with sperm concentration and sperm progressive motility. However, the positive association of serum folate with DFI raises the need for careful prescription of folate supplements. [ABSTRACT FROM AUTHOR]

Graphene nanostructures, exhibiting tunable and nanoscale‐confined mid‐infrared (mid‐IR) plasmons, prevail as a powerful spectroscopic platform for novel surface‐enhanced molecular identification. Particularly, graphene shows exciting opportunities for biosensing applications due to its versatile functionalization methods with different biomolecular building blocks (e.g., enzymes, proteins, and DNA). Here, a quantitative bioassay based on the mid‐IR localized surface plasmon resonance (LSPR) modulation in functionalized graphene nanostructures is demonstrated. Specifically, vitamin B12 (vB12) using the specific recognition elements on modified graphene nanoribbons (i.e., pyrene linkers via π − π stacking + anti‐vB12 antibody fragments via amide bond) is detected. Different concentrations of vB12 spotted on an arrayed panel of a single chip are quantified by the graphene LSPR shifts, where a limit of detection (LOD) of 53.5 ng mL−1 is obtained. The upscaling potential of the bioassay using large area nanostructured graphene films produced by nanoimprinting 2D hole arrays is illustrated. The integration of quantitative bioassay with scalable graphene nanostructures shows promising routes of graphene‐based mid‐IR platforms toward prospective industrial applications. [ABSTRACT FROM AUTHOR]

Maternal folic acid and vitamin B12 (B12) status during pregnancy influence fetal growth. This study elucidated the effect of altered dietary ratio of folic acid and B12 on the regulation of H19/IGF2 locus in C57BL/6 mice. Female mice were fed diets with nine combinations of folic acid and B12 for 4 weeks. They were mated and the offspring born (F1) were continued on the same diet for 6 weeks post-weaning and were allowed to mate. The placenta and fetal (F2) tissues were collected at day 20 of gestation. H19 overexpression observed under dietary deficiency of folate combined with normal B12 (B12 normal folic acid-deficient, BNFD) was associated with an increased expression of microRNA-675 (miR-675) in maternal and fetal tissues. Insulin-like growth factor 2 (IGF2) expression was decreased under folic acid-deficient conditions combined with normal, deficient or over-supplemented state of B12 (BNFD, BDFD and BOFD) in fetal tissues along with B12 deficiency combined with normal folic acid (BDFN) in the placenta. The altered expression of imprinted genes under folic acid-deficient conditions was related to decreased serum levels of folate and body weight (F1). Hypermethylation observed at the H19 differentially methylated region (DMR) (in BNFD) might be responsible for the decreased expression of IGF2 in female fetal tissues. IGF2 DMR2 was found to be hypomethylated and associated with low serum B12 levels with B12 deficiency in fetal tissues. Results suggest that the altered dietary ratio of folic acid and B12 affects the in utero development of the fetus in association with altered epigenetic regulation of H19/IGF2 locus. [ABSTRACT FROM AUTHOR]

Recreational nitrous oxide (N2O) use is widespread, and complications associated with its use are increasingly common. We sought to identify risk factors, clinical features and outcomes in individuals presenting with effects of chronic N2O abuse to develop an approach to clinical assessment and management. A systemic literature review was completed with searches conducted across EMBASE, MEDLINE, PSYCINFO and Cochrane databases. Our search strategy identified 612 studies, 105 met inclusion criteria, and 10 were added via hand search. Subjects from 24 case series and 91 case reports were typically in their 20s, using over 100 bulbs daily for several months. Neurological presentations, including sensory change, gait disturbance or weakness, were characteristic. Serum Vitamin B12 was normal or raised in 133 out of 243 case series subjects and 37 out of 84 reports. Serum homocysteine and methylmalonic acid were usually raised. Macrocytosis and anaemia were not commonly seen. MRI findings were abnormal with dorsal column change where specified, typically involving the cervical spine. Nerve conduction studies mostly reported a sensorimotor polyneuropathy. B12 replacement was the treatment of choice and partial recovery was most reported. This review highlights the dose‐dependent nature of chronic N2O toxicity and recognises functional B12 deficiency as the cause. As B12 is often normal, homocysteine and methylmalonic acid are important biomarkers of disease. An approach to diagnosis is offered but requires validation in prospective studies. Research exploring B12 and methionine therapy is required to refine management. [ABSTRACT FROM AUTHOR]

SUMMARY: This narrative review article aims to update knowledge on the neuropsychiatric complications of nitrous oxide use and low vitamin B12. We consider common forms and uses of nitrous oxide (N2O) and review its mechanism of action, and then explore the potential impacts of use. In particular, neuropsychiatric effects mediated by low vitamin B12 are considered and the correct interpretation of laboratory results explored. This is of particular importance as where vitamin B12 is inactivated by chronic nitrous oxide use, blood test levels of vitamin B12 may not reflect the quantity of functional B12 in patients. [ABSTRACT FROM AUTHOR]

Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS). Considering how vitamin B12 or cobalamin affects the immune system, especially inflammation and the formation of the myelin sheath, it appears as a complementary therapy for MS by affecting some signaling pathways. Recently diagnosed MS patients were divided into two groups (n=30). One group received interferon-beta (IFN-β or Avonex), and another received IFN-β+B12 for six months. Blood samples were taken before and after treatments.  Interleukin (IL)-10 and osteopontin (OPN) levels in the plasma were determined by the enzyme-linked immunosorbent assay (ELISA) method, and the expression of microRNA (miR)-106a, miR-299a, and miR-146a by real-time PCR. IFN-β neither changed the IL-10 plasma levels nor miR106a and miR-299a expression, but it led to a remarkable decrease in OPN concentration and enhancement in let-7c and miR-146a expression. There was a significant decrease in IL-10, OPN plasma levels, miR-106a expression, and a substantial increase in let-7c and  miR-146a expression in IFN-β+B12, treated group. There was no correlation between IL-10 and OPN with related miRNAs in the two treatment groups. Our study indicated that B12 could be a complementary treatment in MS that may influence the disease improvement. [ABSTRACT FROM AUTHOR]

Objectives: Recreational nitrous oxide (N2O) abuse is increasingly popular among youth. We report a systematic clinical, electrophysiological and biological follow-up of patients with neuropathy caused by N2O. Methods: We retrospectively report seven patients with neuropathy attributed to N2O abuse and their comprehensive follow-up. Demographic, toxicological, clinical, biological and electrophysiological data were collected at first and second examination. Functional data were collected at the last evaluation. Results: Seven patients aged 18–30, consuming more than 140 gas-filled balloons (one balloon is filled with approximately 8 g of N2O) per week for over a month, developed a severe, predominantly motor, length-dependent, progressive neuropathy over 3 to 6 weeks. Two-thirds presented associated signs of myelopathy. Distal lower limbs motor deficit and ataxia led to moderate disability. Spinal cord imaging was frequently normal. Nerve conduction studies disclosed an almost exclusively motor axonal neuropathy affecting the lower limbs with active denervation. Homocysteine plasma level was systematically elevated, whereas cobalamin plasma levels were normal in almost all patients. At short-term follow-up after intoxication discontinuation, ataxia and motor deficit only partially resolved despite vitamin B12 supplementation, while active denervation and homocysteinemia decreased. At last follow-up (median 9.2 months, IQR 7.5–10.75), mean ONLS was 2.0 (IQR 2.0–2.0). Discussion: Young patients, with induced N2O motor neuropathy remain disabled after 5 to 14.5 months of gas withdrawal, despite vitamin B12 supplementation. A longer follow-up is needed to fully appraise the severity of these toxic neuropathies. [ABSTRACT FROM AUTHOR]

Background: Gestational diabetes mellitus (GDM) can adversely affect the health of the developing fetus. Women of South Asian origin are particularly at risk of developing GDM. Insulin resistance (IR) contributes to the etiology of GDM, and although studies have shown associations of vitamin B12 (B12) and folate status with GDM and IR, only a limited number of B12 and folate markers have been used.Objective: We used a comprehensive panel of B12 and folate markers to examine their association with IR in pregnant women with diet-controlled GDM and normal glucose tolerance (NGT).Methods: In this cross-sectional study, 59 British-Bangladeshi women (24 GDM and 35 NGT) with a mean age of 29 y, BMI (in kg/m2) 26.7 and gestational age 33 wk were recruited. Serum total B12, holotranscobalamin, folate, methylmalonic acid, plasma homocysteine, 5-methyltetrahydrofolate, and red cell folate (RCF) were measured along with other parameters. The independent sample t-test and chi-squared test were used to assess differences in markers between GDM and NGT women. Spearman's test was used to look for correlations. A simple multiple regression analysis was used to investigate if markers of B12 and folate status predicted IR, using the HOMA-IR and adjusting for age, GDM status, and BMI.Results: There were no differences in concentrations of B12 and folate markers between GDM and NGT women. In Spearman's analysis HOMA-IR correlated negatively with total serum B12 (P < 0.001) and holotranscobalamin (P < 0.05), and positively with BMI (P < 0.001), blood pressure (P < 0.05) and triglycerides (P < 0.05) in all women. MMA did not correlate with any of the B12 markers. In regression analysis, total B12 (β = -0.622, P = 0.004), RCF (β = 0.387, P = 0.018), and BMI (β = 0.024, P < 0.001) were the significant predictors of HOMA-IR variance.Conclusions: Significant associations between markers of B12 and folate status with HOMA-IR were found during the third trimester in British-Bangladeshi women. B12 markers correlated poorly with each other. [ABSTRACT FROM AUTHOR]

Background: Thrombospondin-4 (TSP4) upregulates in the spinal cord following peripheral nerve injury and contributes to the development of neuropathic pain (NP). We investigated the effects of cyanocobalamin alone or in combination with morphine on pain and the relationship between these effects and spinal TSP4 expression in neuropathic rats. Methods: NP was induced by chronic constriction injury (CCI) of the sciatic nerve. Cyanocobalamin (5 and 10 mg/kg/day) was administered 15 days before CCI and then for 4 and 14 postoperative days. Morphine (2.5 and 5 mg/kg/day) was administered only post-CCI. Combination treatment included cyanocobalamin and morphine, 10 and 5 mg/kg/day, respectively. All drugs were administered intraperitoneally. Nociceptive thresholds were detected by esthesiometer, analgesia meter, and plantar test, and TSP4 expression was assessed by western blotting and fluorescence immunohistochemistry. Results: CCI decreased nociceptive thresholds in all tests and induced TSP4 expression on the 4th postoperative day. The decrease in nociceptive thresholds persisted except for the plantar test, and the increased TSP4 expression reversed on the 14th postoperative day. Cyanocobalamin and low-dose morphine alone did not produce any antinociceptive effects. High-dose morphine improved the decreased nociceptive thresholds in the esthesiometer when administered alone but combined with cyanocobalamin in all tests. Cyanocobalamin and morphine significantly induced TSP4 expression when administered alone in both doses for 4 or 14 days. However, this increase was less when the two drugs are combined. Conclusions: The combination of cyanocobalamin and morphine is more effective in antinociception and partially decreased the induced TSP4 expression compared to the use of either drug alone. [ABSTRACT FROM AUTHOR]

As individuals seek increasingly individualised nutrition and lifestyle guidance, numerous apps and nutrition programmes have emerged. However, complex individual variations in dietary behaviours, genotypes, gene expression and composition of the microbiome are increasingly recognised. Advances in digital tools and artificial intelligence can help individuals more easily track nutrient intakes and identify nutritional gaps. However, the influence of these nutrients on health outcomes can vary widely among individuals depending upon life stage, genetics and microbial composition. For example, folate may elicit favourable epigenetic effects on brain development during a critical developmental time window of pregnancy. Genes affecting vitamin B12 metabolism may lead to cardiometabolic traits that play an essential role in the context of obesity. Finally, an individual's gut microbial composition can determine their response to dietary fibre interventions during weight loss. These recent advances in understanding can lead to a more complete and integrated approach to promoting optimal health through personalised nutrition, in clinical practice settings and for individuals in their daily lives. The purpose of this review is to summarise presentations made during the DSM Science and Technology Award Symposium at the 13th European Nutrition Conference, which focused on personalised nutrition and novel technologies for health in the modern world. [ABSTRACT FROM AUTHOR]

Objective: (i) To examine demographic and health characteristics of women of reproductive age on a vegan diet in Australia and compare these to the general population; (ii) to identify sources and intake of vitamin B12 and compare intake to current recommendations and (iii) examine associations between participant characteristics and adequacy of vitamin B12 intake.Design: In this cross-sectional study, data were collected via an online survey. Demographic and health characteristics of women on a vegan diet were compared with women in the general population (using Australian Bureau of Statistics data). Intake of vitamin B12 was estimated using a FFQ and estimation of supplemental intake.Setting: Australia.Participants: Participants (n 1530) were women aged 18-44 years who had been on a vegan diet for at least 6 months.Results: While BMI, smoking habits and intakes of fruit and vegetables compared favourably with the general population, 26 % of respondents had estimated intakes of vitamin B12 below recommendations. Analyses of relationships between vitamin B12 intake and participant characteristics revealed that the strongest predictor of intake was supplementation (P < 0·001); however, 25 % had not supplemented with vitamin B12 in the past 3 months.Conclusions: The vitamin B12 intakes of a substantial proportion of Australian women of reproductive age consuming a vegan diet do not meet the recommended intake, which could adversely affect their health, and, if they are pregnant or lactating, that of their infants too. There is a need for further research in this area to identify effective strategies to address this situation. [ABSTRACT FROM AUTHOR]

Objective: To examine the associations between vitamins of the methionine-homocysteine (Hcys) cycle (B6, B12 and folate) and Hcys with metabolic syndrome (MetS) among Mesoamerican children and their adult parents.Design: We conducted a cross-sectional study. Exposures were plasma vitamins B6 and B12 concentrations, erythrocyte folate and plasma Hcys. In children, the outcome was a continuous metabolic risk score calculated through sex- and age standardisation of waist circumference, the homoeostatic model assessment for insulin resistance, mean arterial pressure (MAP), serum HDL-cholesterol and serum TAG. In parents, the outcome was the prevalence of MetS according to the Adult Treatment Panel III Criteria. We estimated mean differences in the metabolic risk score and prevalence ratios of MetS between quartiles of the exposures using multivariable-adjusted linear and Poisson regression models, respectively.Setting: Capital cities of Belize, Guatemala, El Salvador, the Dominican Republic, Honduras, Nicaragua, Panama, Costa Rica and Chiapas State in Mexico.Participants: In total, 237 school-aged children and 524 parents.Results: Among children, vitamin B12 was inversely associated with the metabolic risk score (quartiles 4-1 adjusted difference = -0·13; 95 % CI: -0·21, -0·04; Ptrend = 0·008) through MAP, HDL-cholesterol and TAG. In contrast, folate was positively associated with the metabolic risk score (quartiles 4-1 adjusted difference = 0·11; 95 % CI: 0·01, 0·20; Ptrend = 0·02). In adults, vitamin B6 was inversely associated with MetS prevalence, whereas vitamin B12 and folate were positively related to this outcome.Conclusions: Vitamins of the methionine-Hcys cycle are associated with MetS in different directions. The associations differ between children and adults. [ABSTRACT FROM AUTHOR]

What is known and objective: B vitamin therapy is a common treatment for diabetic pain and neuropathy, yet its use remains controversial in patients lacking B vitamin deficiencies. The aim of this review was to summarize the current evidence for the efficacy of B vitamin therapy in diabetic patients with neuropathy. Comment: We screened the English literature for clinical studies evaluating B vitamins as a therapy for pain and neuropathy in diabetic patients. We selected 43 relevant studies for qualitative analysis based on our selection criteria. Our survey of the literature revealed substantive heterogeneity with respect to efficacies of reported outcomes, as well as study design. Most beneficial outcomes were reported against baseline measures, with few positive comparisons against placebo. This highlights the need for larger, placebo‐controlled studies. What is new and conclusion: B vitamins should be considered a plausible therapy for diabetic neuropathy, but its overall efficacy remains uncertain and requires further study. [ABSTRACT FROM AUTHOR]

Introduction Megaloblastic anemia is one of the common causes of anemia in India. Duodenal biopsies are routinely performed in the investigation of megaloblastic anemia. The present study was undertaken to analyze the value of duodenal biopsy in megaloblastic anemia and to correlate endoscopic findings with biopsy. As a secondary aim, the study has also analyzed the hematological profile and vitamin B 12 and folate status of these patients. Materials and Methods All the cases of megaloblastic anemia with bone marrow studies diagnosed at PSG Institute of Medical Sciences and Research during the two year period from January 2016 to December 2017 were retrieved. Clinical and laboratory findings (serum vitamin B 12 and folate levels) and endoscopic findings were retrieved from hospital records of the patients. Duodenal biopsies of these patients reported in the histopathology department were retrieved and reviewed. Statistical analysis was done using SPSS software 20.0. Results There were 93 cases of megaloblastic anemia diagnosed on bone marrow biopsies. Tropical sprue was diagnosed in 49.5% of cases, followed by intraepithelial lymphocytosis (17.2%), peptic duodenitis (17.2%), and no significant pathology in 16% of cases. Pancytopenia was present in 54.8% of cases. Isolated vitamin B 12 deficiency including low levels was present in 48.38% and folate deficiency was seen in 4.3% cases; 34.48% cases had both vitamin B 12 and folate deficiency. Conclusion The incidence of tropical sprue in megaloblastic anemia is 49.5% in the study. Duodenal biopsy is valuable in the work up of megaloblastic anemia, irrespective of the endoscopic changes in identifying the etiology. [ABSTRACT FROM AUTHOR]

Background: Studies have shown an association between metformin use and vitamin B12 deficiency. Since 2017, the American Diabetes Association (ADA) Standards of Medical Care in Diabetes Guideline has included a recommendation for periodic vitamin B12 measurements in metformin-treated patients, especially those with anemia or peripheral neuropathy. Objective: To determine the overall incidence and impact of the ADA Guideline on vitamin B12 monitoring in a veteran population on long-term metformin therapy. Methods: Retrospective chart review was performed for patients on metformin who started therapy prior to 2005 at the VA North Texas Health Care System (VANTXHCS). The primary outcome was the proportion of patients with at least 1 vitamin B12 level drawn during 2016 versus 2018. Metformin dose and duration, vitamin B12 supplementation, and incident neuropathy prescriptions or diagnosis were also analyzed. Results: Of 394 patients included for the primary outcome, 136 (34.5%) had at least 1 vitamin B12 level in 2016 versus 198 (50.3%) patients in 2018 (odds ratio: 1.94, P <.001). Of the 394 patients, 157 were diagnosed with neuropathy or prescribed a medication for neuropathy without a vitamin B12 level in the previous year or with a low level that was not supplemented. Conclusion: Vitamin B12 monitoring significantly increased between 2016 and 2018, aligning with the release of the 2017 ADA guidelines. However, a large proportion of patients were identified who were diagnosed with or treated for neuropathy without adequate vitamin B12 monitoring. [ABSTRACT FROM AUTHOR]

Background Elevated plasma methylmalonic acid (MMA) and/or total homocysteine (tHcy), as well as low serum vitamin B12 and/or holotranscobalamin (holoTC) are indicative of vitamin B12 deficiency. Combined indicators (cB12), which pool some or all 4 markers into an index, may be a more reliable diagnostic tool to overcome inconclusive diagnoses with individual markers. Objectives We aimed to describe different cB12 score combinations and estimate the prevalence of low or transitional vitamin B12 status compared with individual markers. Design Using cross-sectional data for B12, MMA, and tHcy in persons ≥20 y participating in NHANES 1999–2004 (n  = 12,335), we examined raw and covariate-adjusted regression models to assess determinants of 3cB12 (all 3 markers) and combinations of 2cB12 (2 markers). Results 3cB12 was significantly associated with B12 (Spearman r  = 0.75), MMA (r = −0.70), and tHcy (r = −0.59). The 3cB12 reference interval (2.5th to 97.5th percentile) was -0.538 to 1.60. In covariate-adjusted models, we found no association of 3cB12 with age; adult females and users of B12 supplements had higher, while adults with advanced chronic kidney disease had lower 3cB12 levels regardless of race-Hispanic origin group (self-reported). Only 2.7% of adults had low or transitional vitamin B12 status using the proposed cB12 cutoff of ≤−0.5, while the prevalence of low (or low-normal) status depended on the selected individual marker and its cutoff: 2.2% and 13% for B12 < 148 and 148–222 pmol/L, respectively; 6.0% for MMA exceeding an age-specific cutoff (250–320 nmol/L); and 8.4% for tHcy > 13 µmol/L. The reference intervals for B12, MMA, and tHcy overlapped from the low (<−2.5) to the transitional (−2.5 to −0.5) and to the adequate (>−0.5) cB12 categories. Conclusions Vitamin B12 deficiency may be overestimated among US adults when individual, conventional markers are used. When only 2 markers are available, the combination of B12 and MMA provides results comparable to 3cB12. [ABSTRACT FROM AUTHOR]

The incidence of gestational diabetes mellitus (GDM) is rising, which warrants attention due to the associated complications during pregnancy and in the long term for both mother and offspring. Studies have suggested a relationship between maternal folate (vitamin B9) and vitamin B12 status and GDM risk. Seemingly the most problematic scenario occurs when there is B-vitamin imbalance, with high folate and low vitamin B12. This nutritional state can occur in vitamin B12 deficient women who exceed the recommended folic acid supplementation. However, the pathological mechanisms behind this relationship are currently unclear and are explored in this review article. A high folate/low B12 can lead to a functional folate deficiency through the methyl-trap phenomenon, impairing re-methylation of homocysteine and regeneration of folates for DNA synthesis and repair. Consequently elevated homocysteine concentration leads to endothelial dysfunction and oxidative stress. Vitamin B12 deficiency also leads to an impairment of the conversion of methylmalonyl-CoA to succinyl-CoA, which has been associated with insulin resistance. Insulin resistance is thought to contribute to the etiology of GDM. More studies are needed to confirm the impact of these and other mechanisms on disease development. However, it highlights a potential avenue for GDM risk modification through a vitamin B12 supplement and improvement of maternal metabolic health. [ABSTRACT FROM AUTHOR]

Background: Assessing the pre- and post-test probability of disease in the context of routine health care is challenging. We wished to study how test performance parameters relating to clinical utility vary by clinical indication in a 'real-world' setting. Methods: The diagnostic accuracy of serum total B12 and Active-B12® (holotranscobalamin) was evaluated in a primary care population, using serum methylmalonic acid as the reference standard. We used electronic requesting to establish the clinical indication for each request. Routine requests from primary care for serum total B12 were included if creatinine was also measured and estimated glomerular filtration rate was at least 60 mL/min/1.73 m2. Results: Clinical indications included peripheral neuropathy (n = 168), anaemia (n = 168), cognitive decline (n = 125), suspected dietary deficiency (n = 76), other (n = 362). For peripheral neuropathy, the area under the receiver operator curve ± 95% confidence interval (AUC ± CI) was 0.63 (0.54–0.71) (P = 0.002) for total B12 and 0.68 (0.60–0.77) (P < 0.0001) for Active-B12®. For anaemia, AUC ± CI was 0.56 (0.47–0.66) (P = 0.10) for total B12 and 0.69 (0.59–0.78) (P < 0.0001) for Active-B12®. For cognitive decline, AUC ± CI was 0.54 (0.43–0.65) (P = 0.26) for total B12 and 0.69 (0.58–0.80) (P = 0.0002) for Active-B12®. The pre–post-test change in probability of disease varied by clinical indication. Conclusion: Combining diagnostic accuracy studies and electronic testing in a 'real-world' setting allows clinical utility to be assessed by clinical indication. Wider application of this would permit more personalised laboratory medicine. In this study, diagnostic performance of total B12 and Active-B12® varied across all indications. Active-B12® provided better discrimination, but this may have reflected the cut-offs used. [ABSTRACT FROM AUTHOR]

Context Some evidence has shown an association between maternal vitamin B12 levels and the development of preeclampsia in pregnant women, but the relationship between preeclampsia and vitamin B12 is not clear. Objective The aim of this systematic review was to compare serum vitamin B12 levels in women with preeclampsia with those in normotensive pregnant women. Data Sources The PubMed/MEDLINE, Scopus, and Web of Science databases were searched up to August 2019, along with the reference lists of included articles. Study Selection The literature was searched for observational studies that investigated vitamin B12 levels in women with preeclampsia. Data Extraction Data were extracted independently by 2 authors. Data were pooled using a random-effects model. Results Vitamin B12 levels in women with preeclampsia were significantly lower than those in healthy women (mean, −15.24 pg/mL; 95%CI, −27.52 to −2.954; P  < 0.015), but heterogeneity between studies was high (I2  = 97.8%; P  = 0.0103). Subgroup analyses based on folic acid supplementation, homocysteine concentrations, and gestational age at the time of sampling for vitamin B12 assessment did not identify the sources of heterogeneity. Conclusions Women with preeclampsia had significantly lower vitamin B12 concentrations than normotensive pregnant women. [ABSTRACT FROM AUTHOR]

Background: Metformin is the first-line drug in the treatment of type 2 diabetes mellitus. Monitoring vitamin B 12 deficiency associated with long-term and high-dose therapy is not a common practice in many clinical settings in Ethiopia. Objective: The study aimed to measure levels of serum vitamin B 12 and folate and to assess the macrocytic status of type 2 diabetes mellitus patients on metformin. Methods: A cross-sectional study was conducted on 80 type 2 diabetes mellitus patients who had been on metformin for 5 months or more at the diabetic clinic of Tikur Anbessa Specialized Teaching Hospital. Serum vitamin B 12 and folate levels were quantified by chemiluminescent immunoassays. Mean corpuscular volume was determined by complete blood count. Differences in vitamin B 12 and folate levels and mean corpuscular volume between different groups were assessed using Kruskal–Wallis H and Mann–Whitney U tests. Results: Vitamin B 12 and folate deficiency were documented in 5% and 23.8% of participants, respectively, and 6.2% of patients were macrocytic. Levels of vitamin B 12 and folate in patients who had been on metformin > 1,500 mg/day ≥ 4 years were significantly lower those who had been on metformin 1,000– 1,500 mg/day and < 1,000 mg/day < 4 years, respectively. Conclusion: Low serum vitamin B 12 and folate levels and macrocytosis were found to be associated with prolonged metformin treatment. [ABSTRACT FROM AUTHOR]

Background and Objective: The causal role of maternal nutrition in orofacial clefts is uncertain. We tested hypotheses that low maternal vitamin B12 and low folate status are each associated with an increased risk of isolated cleft lip with or without cleft palate (CL±P) in a case–control study in Tamil Nadu state, India. Methods: Case-mothers of CL±P children (n = 47) and control-mothers of unaffected children (n = 50) were recruited an average of 1.4 years after birth of the index child and plasma vitamin B12, methylmalonic acid (MMA), total homocysteine (tHcy), and folate were measured at that time. Logistic regression analyses estimated associations between nutrient biomarkers and case–control status. Results: Odds ratios (ORs) contrasting biomarker levels showed associations between case-mothers and low versus high plasma vitamin B12 (OR = 2.48, 95% CI, 1.02-6.01) and high versus low plasma MMA, an indicator of poor B12 status (OR = 3.65 95% CI, 1.21-11.05). Case–control status was not consistently associated with folate or tHcy levels. Low vitamin B12 status, when defined by a combination of both plasma vitamin B12 and MMA levels, had an even stronger association with case-mothers (OR = 6.54, 95% CI, 1.33-32.09). Conclusions: Mothers of CL±P children in southern India were 6.5 times more likely to have poor vitamin B12 status, defined by multiple biomarkers, compared to control-mothers. Further studies in populations with diverse nutritional backgrounds are required to determine whether poor maternal vitamin B12 or folate levels or their interactions are causally related to CL±P. [ABSTRACT FROM AUTHOR]

The occurrence of anorectal malformations (ARM) is thought to be reduced with sufficient folate intake. However, there is no apparent evidence. We focused on enzyme cofactors for one-carbon metabolism, including folate (vitamin B9), vitamin B6 and vitamin B12, and explored the association between maternal combined intake of these B vitamins and the risk of ARM. Using baseline data from a Japanese nationwide birth cohort study between 2011 and 2014, we analysed data of 89 235 women (mean age at delivery = 31·2 years) who delivered singleton live births without chromosomal anomalies. Information on dietary intake was obtained via a FFQ focused on early pregnancy and used to estimate B vitamin intake. We also collected information on the frequency of folic acid supplement use. ARM occurrence was ascertained from medical records. We identified forty-three cases of ARM diagnosed up to the first month after birth (4·8 per 10 000 live births). In terms of individual intake of the respective B vitamins, high vitamin B6 intake was non-significantly associated with reduced odds of ARM. Compared with women in the low combined B vitamin intake group, the OR of having an infant with ARM was 0·4 (95 % CI 0·2, 1·0) in the high intake group (folate ≥400 μg/d, and upper half of vitamin B6 and/or vitamin B12). In conclusion, our cohort analysis suggested an inverse association between the combined intake of one-carbon metabolism-related B vitamins in early pregnancy and ARM occurrence. [ABSTRACT FROM AUTHOR]

Microalgae are not able to produce cobamides (Cbas, B12 vitamers) de novo. Hence, the production of catalytically active Cba-containing methionine synthase (MetH), which is present in selected representatives, is dependent on the availability of exogenous B12 vitamers. Preferences in the utilization of exogenous Cbas equipped with either adenine or 5,6-dimethylbenzimidazole as lower base have been reported for some microalgae. Here, we investigated the utilization of norcobamides (NorCbas) for growth by the Cba-dependent Chlamydomonas reinhardtii mutant strain (Δ metE). The growth yields in the presence of NorCbas were lower in comparison to those achieved with Cbas. NorCbas lack a methyl group in the linker moiety of the nucleotide loop. C. reinhardtii was also tested for the remodeling of NorCbas (e.g. adeninyl-norcobamide) in the presence of different benzimidazoles. Extraction of the NorCbas from C. reinhardtii , their purification, and identification confirmed the exchange of the lower base of the vitamers. However, the linker moiety of the NorCbas nucleotide loop was not exchanged. This observation strongly indicates the presence of an alternative mode of Cba deconstruction in C. reinhardtii that differs from the amidohydrolase (CbiZ)-dependent pathway described in Cba-remodeling bacteria and archaea. [ABSTRACT FROM AUTHOR]

The uncertainty surrounding high intakes of folic acid and associations with cognitive decline in older adults with low vitamin B12 status has been an obstacle to mandatory folic acid fortification for many years. We estimated the prevalence of combinations of low/normal/high vitamin B12 and folate status and compared associations with global cognitive function using two approaches, of individuals in a population-based study of those aged ≥50 years in the Republic of Ireland. Cross-sectional data from 3781 men and women from Wave 1 of The Irish Longitudinal Study on Ageing were analysed. Global cognitive function was assessed by the Mini Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA). Prevalence estimates for combinations of vitamin B12 (plasma vitamin B12 < or ≥258 pmol/l) and folate (plasma folate ≤ or >45·3 nmol/l) concentrations were generated. Negative binomial regression models were used to investigate the associations of vitamin B12 and folate status with global cognitive function. Of the participants, 1·5 % (n 51) had low vitamin B12 (<258 pmol/l) and high folate (>45·3 nmol/l) status. Global cognitive performance was not significantly reduced in these individuals when compared with those with normal status for both B-vitamins (n 2433). Those with normal vitamin B12/high folate status (7·6 %) had better cognitive performance (MMSE: incidence rate ratio (IRR) 0·82, 95 % CI 0·68, 0·99; P = 0·043, MoCA: IRR 0·89, 95 % CI 0·80, 0·99; P = 0·025). We demonstrated that high folate status was not associated with lower cognitive scores in older adults with low vitamin B12 status. These findings provide important safety information that could guide fortification policy recommendations in Europe. [ABSTRACT FROM AUTHOR]

Objectives: To determine Vitamin B12 and Folic Acid Deficiency among Malnourished Children with Pancytopenia. Study Design: Cross-Sectional study. Setting: Department of Pediatric Sheikh Zayed Medical College / Hospital, Rahim Yar Khan. Period: 1st April 2017 to 25th February 2018. Material & Methodology: In this study 60 children having malnutrition and pancytopenia were included. The given performa was filled and record was maintained. Children visiting Paediatric OPD or admitted in the ward having severe malnutrition and pancytopenia in Complete Blood Count were included in the study. While the malnourished Children with normal blood count and children with malignancy e.g; Leukemia, lymphoma etc. were excluded from the study. Results: In this study, mean age of patients was 5 ± 4.2 years, mean weight 10.3± 7.6 kg, mean hemoglobin was 6 ±6.5 g/dl, mean folic acid was 7.7± 6.7 (median 5.6) and mean vitamin B12 563± 537(median 367). Out of total 37 (61.7 %) were male. In this study, grade I malnutrition was 2 (3.3 %), grade II, 17 (28.3%) and grade III, 41(68.3%). Conclusion: Vitamin B 12 & Folic Acid deficiency is found to be a major factor of bone marrow suppression in malnourished children and our result showed that folic acid deficiency was significantly low in females and Vitamin B12 in males. [ABSTRACT FROM AUTHOR]

Prenatal folate and vitamin B12 status have been linked to child neuropsychological development, but less is known about maternal genetic influences on this association. We conducted an exploratory longitudinal study of 181 mother–child pairs to assess whether maternal MTHFR 677C>T genotype modifies the association between maternal plasma folate and vitamin B12 in the first trimester of pregnancy and child neuropsychological development. Maternal plasma folate and vitamin B12 were determined by radioimmunoassay, and MTHFR 677C>T genotypes by PCR. We evaluated child neuropsychological development at 1, 3, 6, 12, 18, 24, and 30 month old using the Bayley Scales of Infant Development II. We analyzed the data using mixed-effects multivariate linear regression. The MTHFR 677C>T genotype distribution among the mothers was 18.2% CC, 49.8% CT, and 32.0% TT. The Mental Development Index (MDI) was inversely associated with maternal plasma folate among offspring of MTHFR 677CC mothers (β = -2.18 per twofold increase, 95% CI -4.07; -0.30, corrected P value = 0.02); no significant associations were observed among children born to women of other genotypes. The Motor Development Index (PDI) was not significantly associated with maternal plasma folate in any maternal MTHFR 677C>T genotype group, nor were MDI or PDI significantly associated with maternal plasma vitamin B12 in any maternal MTHFR 677C>T genotype group. This study suggests that maternal MTHFR 677CC genotype interacts with first-trimester plasma folate to influence offspring mental development. [ABSTRACT FROM AUTHOR]

High cobalamin levels have previously been associated with short-term cancer risk, including lung cancer. We explored whether levels of cobalamin and/or its binding proteins are useful as a diagnostic tool in patients suspected of non-small cell lung cancer. We included 889 patients referred for fast-track diagnosis of lung cancer to Aarhus University Hospital, Denmark. We analyzed plasma concentrations of cobalamin, transcobalamin, holotranscobalamin and haptocorrin. Information on lung cancer diagnosis was retrieved from a national database. The study cohort showed levels above reference intervals for cobalamin 12%, holotranscobalamin 25%, transcobalamin 9% and haptocorrin 36% (all p-values <.05). We observed no difference in cobalamin or holotranscobalamin levels when comparing patients diagnosed with non-small cell lung cancer (n = 161, 18%) to patients without lung cancer (n = 742, 80%), while transcobalamin showed minor differences. Haptocorrin was significantly higher in those with cancer, mainly among patients with adenocarcinoma (n = 94). A comparison of patients with the highest vs. lowest quartile levels of haptocorrin yielded an adjusted odds ratio for adenocarcinoma of 2.39 (95% confidence interval: 1.26-4.55). However, ROC curve analyzes showed haptocorrin (AUC = 0.55) and total transcobalamin (AUC = 0.56) to be poor diagnostic markers for lung cancer. A high proportion of patients suspected for non-small cell lung cancer showed increased levels of cobalamin-binding proteins. We thereby confirm the association between non-small cell lung cancer and high cobalamin levels and found that haptocorrin was the major underlying factor causing high cobalamin levels. However, none of these biomarkers were of diagnostic use among patients referred for suspected lung cancer. [ABSTRACT FROM AUTHOR]

Rapid selection of a genetic variant that confers continuous life-long lactase production in Europeans (LCT-13910 C/T) has been attributed to the advantages of acquiring nutrients from consuming milk without the disadvantages of lactose malabsorption. Individuals with this genetic lactase persistence (LP) variant generally consume more milk and have been shown to have higher levels of serum vitamin D. Vitamin D is the principal regulator of Ca absorption and its synthesis in skin is dependent on UVB exposure. The primary aim of the present study was to compare serum vitamin D concentrations with LP variant and to control for UVB exposure. Data from over 100 000 individuals living in Norway, a country with low UVB exposure, was retrospectively retrieved for comparison of genetic LP variant, serum 25-hydroxyvitamin D (25(OH)D) concentration and the time of year when serum samples were taken. For comparison, a similar analysis was performed with a natural dairy micronutrient, namely vitamin B12. It was found that individuals with the genetic LP variant had considerably higher levels of serum 25(OH)D (P < 2 × 10−16, Cohen's d = 0·73) but lower levels of vitamin B12 (P < 2 × 10−16, Cohen's d = 0·11), compared with genetic lactase non-persistent individuals, even when controlled for seasonality, age and sex. The difference in serum 25(OH)D levels did not diminish in summer months, showing the role of vitamin D in LP variant selection in areas of low UVB irradiation. LP variant selection advantage through acquiring another dairy micronutrient, vitamin B12, was not observed. [ABSTRACT FROM AUTHOR]

Background: Vitamin B12 deficiency is a common disorder. In circulation, vitamin B12 is bound to transcobalamin (holotranscobalamin), which is considered the active form of cobalamin. The objective of this study was to evaluate the analytical performance of the Roche Elecsys Active B12 immunoassay. Methods: Limit of quantification and linearity were assessed according to CLSI EP17-A2 and EP-6A guidelines. Precision and bias of Roche Active B12 test against Architect ci8200 (Abbott) were performed according to CLSI EP-5 A3 guideline at three European laboratories. Precision requirements were set at <4% for within-run precision and <15% for intermediate precision. Requirements for method comparison were set at a slope of 1.00 ± 20%. In addition, 95% reference interval was conducted in European adults according to CLSI-EP28 guideline. Results: The assay was shown to be linear and precise and met the requirements. Lot-to-lot variation and lab-to-lab variation both were ≤4%. Method comparison with Abbott Architect showed a significant bias of 9 pmol/L, which increases to up to 23 pmol/L around the current medical decision point. The 95% reference interval of the Roche Elecsys Active B12 test was determined at 37–188 pmol/L. Conclusion: Although Roche Elecsys Active B12 immunoassay met the requirements, this test has a positive bias of 9 pmol/L, which led to an increase in lower limit of reference interval compared with Abbott test. This test first needs to be clinically validated before it can be applied as a first-line screening test in the diagnosis of vitamin B12 deficiency. [ABSTRACT FROM AUTHOR]