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Although most organisms synthesize methionine from homocysteine and methyl folates, some have "core" methionine synthases that lack folate-binding domains and use other methyl donors. In vitro, the characterized core synthases use methylcobalamin as a methyl donor, but in vivo, they probably rely on corrinoid (vitamin B12-binding) proteins. We identified four families of core methionine synthases that are distantly related to each other (under 30% pairwise amino acid identity). From the characterized enzymes, we identified the families MesA, which is found in methanogens, and MesB, which is found in anaerobic bacteria and archaea with the Wood-Ljungdahl pathway. A third uncharacterized family, MesC, is found in anaerobic archaea that have the Wood-Ljungdahl pathway and lack known forms of methionine synthase. We predict that most members of the MesB and MesC families accept methyl groups from the iron-sulfur corrinoid protein of that pathway. The fourth family, MesD, is found only in aerobic bacteria. Using transposon mutants and complementation, we show that MesD does not require 5-methyltetrahydrofolate or cobalamin. Instead, MesD requires an uncharacterized protein family (DUF1852) and oxygen for activity.

The beneficial human gut bacterium Akkermansia muciniphila provides metabolites to other members of the gut microbiota by breaking down host mucin, but most of its other metabolic functions have not been investigated. A. muciniphila strain MucT is known to use cobamides, the vitamin B12 family of cofactors with structural diversity in the lower ligand. However, A. muciniphila MucT is unable to synthesize cobamides de novo, and the specific forms that can be used by A. muciniphila have not been examined. We found that the levels of growth of A. muciniphila MucT were nearly identical with each of seven cobamides tested, in contrast to nearly all bacteria that had been studied previously. Unexpectedly, this promiscuity is due to cobamide remodeling-the removal and replacement of the lower ligand-despite the absence of the canonical remodeling enzyme CbiZ in A. muciniphila We identified a novel enzyme, CbiR, that is capable of initiating the remodeling process by hydrolyzing the phosphoribosyl bond in the nucleotide loop of cobamides. CbiR does not share similarity with other cobamide remodeling enzymes or B12-binding domains and is instead a member of the apurinic/apyrimidinic (AP) endonuclease 2 enzyme superfamily. We speculate that CbiR enables bacteria to repurpose cobamides that they cannot otherwise use in order to grow under cobamide-requiring conditions; this function was confirmed by heterologous expression of cbiR in Escherichia coli Homologs of CbiR are found in over 200 microbial taxa across 22 phyla, suggesting that many bacteria may use CbiR to gain access to the diverse cobamides present in their environment.IMPORTANCE Cobamides, comprising the vitamin B12 family of cobalt-containing cofactors, are required for metabolism in all domains of life, including most bacteria. Cobamides have structural variability in the lower ligand, and selectivity for particular cobamides has been observed in most organisms studied to date. Here, we discovered that the beneficial human gut bacterium Akkermansia muciniphila can use a diverse range of cobamides due to its ability to change the cobamide structure via a process termed cobamide remodeling. We identify and characterize the novel enzyme CbiR that is necessary for initiating the cobamide remodeling process. The discovery of this enzyme has implications for understanding the ecological role of A. muciniphila in the gut and the functions of other bacteria that produce this enzyme.

BackgroundPotential safety concerns relative to impaired cognitive function may exist when high folic acid exposures are combined with low vitamin B-12 status.ObjectivesWe aimed to examine the relation of the coexistence of high folate and low vitamin B-12 status with cognitive function, utilizing various definitions of "high" folate status.MethodsCross-sectional data from older adults (≥60 y; n = 2420) from the 2011-2014 NHANES were analyzed. High folate status was defined as unmetabolized serum folic acid (UMFA) > 1 nmol/L or serum total folate > 74.1 nmol/L, and low vitamin B-12 status as methylmalonic acid > 271 nmol/L or serum vitamin B-12

BackgroundThere is conflicting evidence in the literature on the association between (elevated) serum B12 concentrations and subsequent disease or mortality. We evaluated in the NHANES general population the association of serum B12 concentrations as well as vitamin B12 supplement intake with all-cause, cardiovascular, and cancer-related mortality, while taking into account demographic and lifestyle factors and significant other diseases which are known to be associated with poorer outcome.MethodsThe main outcomes of our study were all-cause mortality, cardiovascular mortality, and cancer-related mortality. Mortality status and cause of death were determined by NHANES-linked National Death Index public access files through December 31, 2015. The association of serum B12 concentrations and vitamin B12 supplement intake with mortality was assessed with Cox proportional hazard (PH) models, with adjustment for a number of relevant demographic and lifestyle factors and comorbidity.ResultsThe final study population of 24,262 participants had a mean age of 48 (SD 19) years; 50.1% were males. The median follow-up duration was 109 months (range 1-201 months). On the census day of December 31, 2015, 3023 participants were determined as deceased (12.5%). The fully adjusted Cox PH model indicated that low serum B12 concentrations  700 pmol/l were associated with an increase in cardiovascular mortality only (HR 1.45, 95% CI 1.01-2.06, p = 0.042). Participants with a diagnosis of hypertension, dyslipidemia, CVD, and cancer more frequently used vitamin B12-containing supplements than those without these diagnoses. We could not demonstrate an association between vitamin B12 supplement intake and mortality, when adjusted for comorbidity.ConclusionsIn the general population of NHANES, low serum B12 concentrations were associated with a moderate increase in all-cause mortality. There was a small but significant increase in cardiovascular mortality in the groups with low or high serum B12. High intake of vitamin B12 in the form of supplements was not associated with any adverse effect on mortality and therefore can be regarded as safe.

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/Aim. Previous studies showed that mild cognitive impairment (MCI) was more common in patients with comorbidities and those using medications that disrupt the homeostasis of vitamin B12. The aim of our study was to determine which of these factors are significantly associated with MCI, as well as which are the most significant risk factors for predicting its occurrence. Methods. The data have been prospectively collected for 200 adults (35-65 years old) in primary care settings enrolled in the clinical study with the case-control approach. Results. By applying the X2 test for independence, we have determined that the MCIs and the use of proton-pump inhibitors (PPIs) (p < 0.0005), as well as metformin (p < 0.0005), are independent factors. In addition, a significantly higher percentage of subjects who had MCI also had a peptic ulcer and diabetes mellitus type 2 (T2DM). Direct logistic regression has been implemented in order to estimate the influence of many probability factors on whether the study patients would have the MCI. Two variables made statistically significant contributions to the model, and these are the serum concentrations of vitamin B12 [odds ratio (OR) = 0.953; 95% confidence interval (CI) 0.936-0.971; p < 0.001] and T2DM (OR = 6.681; 95% CI 1.305-34.198; p = 0.023). Conclusion. The absolute and relative risk associations of exposure to medicines and MCI is lower than those of comorbidities and MCI. Serum concentrations of vitamin B12, as well as the presence of T2DM, have the greatest statistically significant influence on predicting MCI. [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]

The pathophysiology of sickle cell disease (SCD) includes vasculopathy as well as anaemia. Elevated plasma homocysteine is a risk factor for vascular disease and may be associated with increased risk of vascular complications in SCD patients. In the present study, microvascular characteristics were assessed in the bulbar conjunctiva of 18 paediatric and 18 adult SCD patients, using the non-invasive technique of computer-assisted intravital microscopy. A vasculopathy severity index (SI) was computed to quantify the degree of microvasculopathy in each patient. Plasma homocysteine and several of its determinants [serum folate and vitamin B12, plasma pyridoxal-5'-phosphate (vitamin B6 status) and creatinine (kidney function)] were measured. Age was strongly correlated with microvasculopathy in the SCD patients, with the SI increasing about 0·1 unit per one-year increase in age (P

Carnitine, a molecule found in red meat, is metabolized to trimethylamine (TMA) by the gut microbiota. TMA is then converted in the liver to trimethylamine oxide, a causative agent for atherosclerosis. Kountz et al have discovered an alternative pathway for carnitine metabolism in the gut bacterium Eubacterium limosum Instead of forming TMA, carnitine is demethylated by the newly discovered methyltransferase MtcB, sending one-carbon units into production of short-chain fatty acids. These results suggest that bacterial metabolic activities could promote cardiovascular health by preventing the buildup of toxin precursors.

BackgroundUsing blood specimens from untreated early Parkinson's disease (PD) patients from the DATATOP trial, we found that subjects in the low serum vitamin B12 tertile experienced greater annualized change in ambulatory capacity score, whereas those with moderately elevated (>15 μmol/L) total homocysteine had greater annualized declines in the Mini-Mental State Exam.MethodsIn this this study we sought to determine whether levels of cerebrospinal fluid (CSF) B12 markers were also associated with progression of PD.ResultsThe annualized change in the UPDRS "walking" item, a component of the ambulatory capacity score, was worse in the low B12 tertile. No association with change in the Mini-Mental State Exam was seen for those 7% with the highest baseline CSF total homocysteine.ConclusionsIn these untreated early-PD subjects, low CSF B12 predicted greater worsening of the UPDRS "walking" item, whereas CSF total homocysteine was not associated with progression of cognitive impairment. These findings extend and partially support our findings in serum. © 2020 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.

Despite very low concentrations of cobalt in marine waters, cyanobacteria in the genus Prochlorococcus retain the genetic machinery for the synthesis and use of cobalt-bearing cofactors (cobalamins) in their genomes. We explore cobalt metabolism in a Prochlorococcus isolate from the equatorial Pacific Ocean (strain MIT9215) through a series of growth experiments under iron- and cobalt-limiting conditions. Metal uptake rates, quantitative proteomic measurements of cobalamin-dependent enzymes, and theoretical calculations all indicate that Prochlorococcus MIT9215 can sustain growth with less than 50 cobalt atoms per cell, ∼100-fold lower than minimum iron requirements for these cells (∼5,100 atoms per cell). Quantitative descriptions of Prochlorococcus cobalt limitation are used to interpret the cobalt distribution in the equatorial Pacific Ocean, where surface concentrations are among the lowest measured globally but Prochlorococcus biomass is high. A low minimum cobalt quota ensures that other nutrients, notably iron, will be exhausted before cobalt can be fully depleted, helping to explain the persistence of cobalt-dependent metabolism in marine cyanobacteria.

BackgroundHuman milk vitamin B12 (B12) concentrations depend on maternal status and intake; only few data are available in high-income countries.ObjectiveWe assessed human milk B12 concentrations during the first 6 months postpartum in Norwegian women and its association with maternal dietary B12 intake and maternal urinary methylmalonic acid (MMA) concentration.MethodsIn this cross-sectional study, 175 mothers, exclusively (80%) or partially (20%) breastfeeding, were included. Milk B12 was measured by IMMULITE®/IMMULITE® 1000 B12 competitive protein binding assay and urinary MMA relative to creatinine (MMA/Cr) by liquid chromatography-tandem-mass spectrometry. Maternal habitual B12 intake and supplement use were estimated using a food frequency questionnaire.ResultsMean human milk B12 concentration was 327 pmol/L (range 140-1089), with 402 pmol/L at 1 month (n = 21), 333 pmol/L at four months (n = 32), and 299 pmol/L at 6 months (n = 21). Maternal B12 intake was 5 µg/d, 89% met the Estimated Average Requirement, and supplement use did not affect milk B12 concentrations. MMA/Cr was low in all women compared with published data. In exclusively breastfeeding women, MMA/Cr (beta (95% CI) -42.5 (-82.5, -2.5) and time since birth (-4.9 (-9.6, -0.3)) were significant predictors of human milk B12 concentrations. There was no association between total B12 intake and milk B12 concentration or between total B12 intake and MMA/Cr.ConclusionsMaternal B12 status and human milk B12 concentrations are likely sufficient, based on adequate maternal B12 dietary intake combined with low urinary MMA concentrations. Nevertheless, milk B12 concentration fell during 6 months postpartum while maternal B12 status did not change.

Clostridioides (Clostridium) difficile is an opportunistic pathogen known for its ability to colonize the human gut under conditions of dysbiosis. Several aspects of its carbon and amino acid metabolism have been investigated, but its cobamide (vitamin B12 and related cofactors) metabolism remains largely unexplored. C. difficile has seven predicted cobamide-dependent pathways encoded in its genome in addition to a nearly complete cobamide biosynthesis pathway and a cobamide uptake system. To address the importance of cobamides to C. difficile, we studied C. difficile 630 Δerm and mutant derivatives under cobamide-dependent conditions in vitro Our results show that C. difficile can use a surprisingly diverse array of cobamides for methionine and deoxyribonucleotide synthesis and can use alternative metabolites or enzymes, respectively, to bypass these cobamide-dependent processes. C. difficile 630 Δerm produces the cobamide pseudocobalamin when provided the early precursor 5-aminolevulinic acid or the late intermediate cobinamide (Cbi) and produces other cobamides if provided an alternative lower ligand. The ability of C. difficile 630 Δerm to take up cobamides and Cbi at micromolar or lower concentrations requires the transporter BtuFCD. Genomic analysis revealed genetic variations in the btuFCD loci of different C. difficile strains, which may result in differences in the ability to take up cobamides and Cbi. These results together demonstrate that, like other aspects of its physiology, cobamide metabolism in C. difficile is versatile.IMPORTANCE The ability of the opportunistic pathogen Clostridioides difficile to cause disease is closely linked to its propensity to adapt to conditions created by dysbiosis of the human gut microbiota. The cobamide (vitamin B12) metabolism of C. difficile has been underexplored, although it has seven metabolic pathways that are predicted to require cobamide-dependent enzymes. Here, we show that C. difficile cobamide metabolism is versatile, as it can use a surprisingly wide variety of cobamides and has alternative functions that can bypass some of its cobamide requirements. Furthermore, C. difficile does not synthesize cobamides de novo but produces them when given cobamide precursors. A better understanding of C. difficile cobamide metabolism may lead to new strategies to treat and prevent C. difficile-associated disease.

Increased first-trimester low-density lipoprotein (LDL-C) concentration has been associated with adverse pregnancy outcomes, such as gestational diabetes. The B vitamins folate, B-6, and total B-12 are key for the methyl group-dependent endogenous synthesis of phosphatidylcholine, which is needed for lipoprotein synthesis, e.g., very low-density lipoprotein (VLDL), the precursor of circulating LDL-C. Maternal B-vitamin concentration usually declines across trimesters. Whether changes in maternal B-vitamin concentrations are associated with total cholesterol (TC), triglycerides (TG), and lipoprotein concentrations is unknown. Therefore, we explored the association between plasma folate, vitamin B-6 in the form of pyridoxal 5'-phosphate (PLP), and total B-12 with serum TC, LDL-C, HDL-C, and TG concentrations across trimesters. This secondary analysis used data of a prospective pregnancy cohort study included apparently healthy adult women (n = 179) from Rio de Janeiro, Brazil. The biomarkers were measured in fasting blood samples collected at 5-13, 20-26, and 30-36 weeks of gestation. The associations between B vitamins and lipid concentrations across trimesters were explored using linear mixed-effect models. Among B vitamins, only plasma folate was positively associated with TC (β = 0.244, 95% CI 0.034-0.454) and LDL-C (β = 0.193, 95% CI 0.028-0.357) concentrations. The positive relationship of maternal folate and TC and LDL-C concentrations may indicate the importance of folate as a methyl donor for lipoprotein synthesis during pregnancy.

Rare plants that contain corrinoid compounds mostly comprise cobalamin analogues, which may compete with cobalamin (vitamin B12 (B12)) metabolism. We examined the presence of B12 in a cultivated strain of an aquatic plant: Wolffia globosa (Mankai), and predicted functional pathways using gut-bioreactor, and the effects of long-term Mankai consumption as a partial meat substitute, on serum B12 concentrations. We used microbiological assay, liquid-chromatography/electrospray-ionization-tandem-mass-spectrometry (LC-MS/MS), and anoxic bioreactors for the B12 experiments. We explored the effect of a green Mediterranean/low-meat diet, containing 100 g of frozen Mankai shake/day, on serum B12 levels during the 18-month DIRECT-PLUS (ID:NCT03020186) weight-loss trial, compared with control and Mediterranean diet groups. The B12 content of Mankai was consistent at different seasons (p = 0.76). Several cobalamin congeners (Hydroxocobalamin(OH-B12); 5-deoxyadenosylcobalamin(Ado-B12); methylcobalamin(Me-B12); cyanocobalamin(CN-B12)) were identified in Mankai extracts, whereas no pseudo B12 was detected. A higher abundance of 16S-rRNA gene amplicon sequences associated with a genome containing a KEGG ortholog involved in microbial B12 metabolism were observed, compared with control bioreactors that lacked Mankai. Following the DIRECT-PLUS intervention (n = 294 participants; retention-rate = 89%; baseline B12 = 420.5 ± 187.8 pg/mL), serum B12 increased by 5.2% in control, 9.9% in Mediterranean, and 15.4% in Mankai-containing green Mediterranean/low-meat diets (p = 0.025 between extreme groups). Mankai plant contains bioactive B12 compounds and could serve as a B12 plant-based food source.

Nutrient interventions initiated after conception tend to have modest effects on maternal nutritional status and pregnancy outcomes. Thus, we compared the association between micronutrient intakes and the trajectories of their biomarkers before and during pregnancy. Data from a randomized trial of the effect of a nutrient-rich, food-based supplement given to 317 Vietnamese women prior to or during pregnancy on birth outcomes were used to assess nutrient intakes with biomarker trajectories of zinc, iron, folate, cobalamin, and vitamin A using linear mixed regression models. The circulating plasma or serum trajectories of all five micronutrients were associated to their baseline levels (p < 0.0001). Plasma zinc trajectories were also related to farm work (p = 0.024). Cobalamin and vitamin A trajectories were associated with gestational weight gain (p = 0.003 and p = -0.037, respectively). In this population of rural Vietnamese women, nutrient intakes during pregnancy did not affect biomarker trajectories. The primary determinant of each nutrient biomarker trajectory was its respective baseline level prior to conception.

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]

Traditionally, the bioavailability of vitamin B-12 (B12) from in vivo labeled foods was determined by labeling the vitamin with radiocobalt (57Co, 58Co or 60Co). This required use of penetrating radioactivity and sometimes used higher doses of B12 than the physiological limit of B12 absorption. The aim of this study was to determine the bioavailability and absorbed B12 from chicken eggs endogenously labeled with 14C-B12 using accelerator mass spectrometry (AMS). 14C-B12 was injected intramuscularly into hens to produce eggs enriched in vivo with the 14C labeled vitamin. The eggs, which provided 1.4 to 2.6 μg of B12 (~1.1 kBq) per serving, were scrambled, cooked and fed to 10 human volunteers. Baseline and post-ingestion blood, urine and stool samples were collected over a one-week period and assessed for 14C-B12 content using AMS. Bioavailability ranged from 13.2 to 57.7% (mean 30.2 ± 16.4%). Difference among subjects was explained by dose of B12, with percent bioavailability from 2.6 μg only half that from 1.4 μg. The total amount of B12 absorbed was limited to 0.5-0.8 μg (mean 0.55 ± 0.19 μg B12) and was relatively unaffected by the amount consumed. The use of 14C-B12 offers the only currently available method for quantifying B12 absorption in humans, including food cobalamin absorption. An egg is confirmed as a good source of B12, supplying approximately 20% of the average adult daily requirement (RDA for adults = 2.4 μg/day).

Allosteric regulation of methylmalonyl-CoA mutase (MCM) by the G-protein chaperone CblA is transduced via three "switch" elements that gate the movement of the B12 cofactor to and from MCM. Mutations in CblA and MCM cause hereditary methylmalonic aciduria. Unlike the bacterial orthologs used previously to model disease-causing mutations, human MCM and CblA exhibit a complex pattern of regulation that involves interconverting oligomers, which are differentially sensitive to the presence of GTP versus GDP. Patient mutations in the switch III region of CblA perturb the nucleotide-sensitive distribution of the oligomeric complexes with MCM, leading to loss of regulated movement of B12 to and/or from MCM and explain the molecular mechanism of the resulting disease.