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Objectives: Alzheimer's disease (AD) is a devastating neurodegenerative disorder with a complex aetiology. The aims of this study were to investigate the relationship between vitamin B supplementation and AD risk and to explore the potential mediating effect of the gut microbiota in this relationship., Methods: We employed a Mendelian randomisation analysis to examine the association between different vitamin B supplementation modalities (vitamin B 6 , folic acid, B 12 , and vitamin B complex tablets) and AD risk. Univariate Mendelian randomisation with inverse-variance weighting was used. Additionally, mediation analyses were conducted to identify the potential mediating effects of 119 known bacterial genera., Results: The univariate Mendelian randomisation analyses showed no significant direct associations between individual vitamin B supplements or vitamin B complex tablets and AD risk. However, several gut bacterial genera were significantly associated with AD risk. Lachnospiraceae (NK4A136 group), Paraprevotella, Slackia, and Bifidobacterium were associated with reduced AD risk, while Defluviitaleaceae (UCG011), Desulfovibrio , Eubacterium ventriosum group, and Ruminococcaceae UCG-003 were associated with increased AD risk. The mediation analysis revealed that Lachnospiraceae (NK4A136 group), Defluviitaleaceae (UCG011), and Bifidobacterium fully mediated the causal relationships between vitamin B 12 , B 6 , and B complex supplementation, respectively, and AD risk., Conclusions: This study provides evidence suggesting that certain gut microbiota genera are significantly associated with AD risk and may mediate the relationship between vitamin B supplementation and AD risk. These findings offer new insights into the variable effectiveness of B vitamins in treating neurodegenerative diseases and suggest potential new strategies for AD treatment and prevention.

Purpose: To investigate the bioavailability of vitamin B 12 from nori and to evaluate the required dosage for improving vitamin B 12 nutritional status in vegetarians not using supplements., Methods: The study design is an open-label, parallel, dose-response randomized controlled trial. Thirty vegetarians were assigned to control (no nori), low-dose (5 g nori, aiming to provide 2.4 µg vitamin B 12 per day), or high-dose (8 g nori, aiming to provide 4 µg vitamin B 12 per day) groups. The primary outcome was changes in vitamin B 12 status as measured by serum vitamin B 12 , holotranscobalamin (holoTC), homocysteine (Hcy), and methylmalonic acid (MMA), and a combined score of these four markers (4cB12 score) during the four-week intervention. Dietary vitamin B 12 intakes were assessed at baseline and end of the trial with a 17-item food frequency questionnaire designed for vitamin B 12 assessment. General linear model was used to compare least square means of changes in each biomarker of vitamin B 12 status, among the three groups, while adjusting for respective baseline biomarker., Results: After adjusting for baseline status, nori consumption led to significant improvement in serum vitamin B 12 (among-group P-value = 0.0029), holoTC (P = 0.0127), Hcy (P = 0.0225), and 4cB12 (P = 0.0094). Changes in MMA did not differ significantly across groups, but showed within-group pre-post improvement in the low-dose group (median [p25, p75] = -339 [-461, -198] nmol/L). Vitamin B 12 status appeared to plateau at low dose (5 g of nori), which compared with control group, improved serum vitamin B 12 (lease square mean [95% CI] = + 59 [25, 93] pmol/L, P = 0.0014); holoTC (+ 28.2 [10.1, 46.3] pmol/L, P = 0.0035); Hcy (-3.7 [-6.8, -0.6] µmol/L, p = 0.0226); and 4cB12 score (+ 0.67 [0.24, 1.09], p = 0.0036). High-dose resulted in similar improvements. There was no significant difference between low-dose and high-dose groups in all biomarkers of vitamin B 12 ., Conclusions: Consuming 5 g of nori per day for 4 weeks significantly improved vitamin B 12 status in vegetarians. A higher dose (8 g) may not confer additional benefits., Clinical Trial Registration: ClinicalTrials.gov Identifier: NCT05614960. Date of registration: November 14th 2022., (© 2024. The Author(s).)

Vitamin B 12 is a water-soluble vitamin with a complex chemical structure. It can participate in the synthesis and repair of DNA in the human body and plays an important role in regulating the nervous system. The deficiency of vitamin B 12 will lead to megaloblastic anemia and neuropathy. Traditionally, animal foods have been the main dietary source of vitamin B 12 . However, this review points to certain plant sources (such as algae, mushrooms, fermented vegetables, and fermented beans) as viable vitamin B 12 supplements for vegetarians. These sources validate our initial hypothesis that a plant-based diet can adequately provide essential nutrients previously thought to be available only through animal products. In terms of quantification, since the content of vitamin B 12 in food samples is low and is easily interfered by impurities, highly sensitive and specific analytical methods are used for the quantification of vitamin B 12 . The findings from this review could be instrumental in developing fortified plant-based foods that could prevent B 12 deficiency in vegetarians and vegans, thereby broadening the scope of nutritional options available to those on plant-based diets., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Purpose: To assess vitamin D, folate, vitamin B 12 , and iron status in Old Order Anabaptist (OOA) pregnant/postpartum women. Methods: Blood was analyzed for plasma 25 hydroxy vitamin D (25(OH)D), red blood cell (RBC) folate, serum vitamin B 12 , and iron status indicators. Dietary intakes (food and supplements) from 3-day estimated records were compared to Dietary Reference Intakes and Canada's Food Guide (2007). Results: Fifty women participated in this descriptive cross-sectional study. Concentrations of 25(OH)D were low (<50 nmol/L for 20% and < 75 nmol/L for 63%); 42% had total vitamin D intakes < estimated average requirement (EAR). All women had RBC folate above the 1360 mmol/L cut-off. Nineteen percent had folate intakes upper limit. One woman had low serum vitamin B 12 (<148 pmol/L); serum vitamin B 12 was high (>652 pmol/L) for 24%. None had vitamin B 12 intakes 12 . These findings provide guidance to ensure appropriate dietary and supplement intakes in this potentially vulnerable and rarely studied population.

Background & Aims: Metformin is a widely prescribed first line drug for the treatment of type 2 diabetes mellitus (DM). Studies have shown that the use of metformin is often associated with a decrease in vitamin B 12 (B 12 ) levels in patients with DM. Few studies have shown that this effect could be mitigated with calcium supplementation. In the present study, we quantified the effect of metformin, and metformin co-administered with calcium on B 12 absorption using a novel stable isotope [ 13 C] cyanocobalamin tracer., Methods: A pilot crossover study was conducted to estimate the bioavailability of B 12 in healthy subjects, using [ 13 C] cyanocobalamin as a tracer. In the study, [ 13 C] cyanocobalamin was administered orally to the participants followed by hourly venous sampling to measure the concentration of the tracer and estimate bioavailability. This protocol was followed for three experiment days, each separated by a one month wash out period. As part of the study, all participants received the tracer alone for the control day (C), metformin 850 mg along with the tracer for the metformin day (M) and metformin 850 mg with calcium 500 mg and the tracer for the metformin calcium day (MC)., Results: Seven participants completed all three experiment days. The mean B 12 bioavailability (±SD, n = 7) was 42.6 ± 10.2% for the control day (C), 30.8 ± 15.3% for the metformin day (M) and 46.4 ± 8.6% for the metformin-calcium day (MC). Repeated measures ANOVA was done and the pairwise comparison showed a significant difference in the B 12 bioavailability between control and metformin day (C vs M p = 0.010), and between the metformin and metformin with calcium day (M vs MC p = 0.003)., Conclusion: B 12 bioavailability reduced significantly from baseline (C) when metformin (M) was administered and this reduction was reversed when calcium was co-administered (MC) in healthy participants. In patients using metformin, calcium supplementation as a strategy to prevent B 12 deficiency needs to be further studied., Competing Interests: Declaration of competing interest No potential conflicts of interests to declare., (Copyright © 2024 European Society for Clinical Nutrition and Metabolism. Published by Elsevier Ltd. All rights reserved.)

Background: Vitamin B 12 is essential for deoxyribonucleic acid synthesis and genome stability. A deficiency of vitamin B 12 is associated with telomere shortening, genomic aging, and increased risk of chronic disease and mortality., Objectives: The study aims to determine the effect of vitamin B 12 supplementation on leukocyte telomere length (LTL) in infants at risk of vitamin B 12 deficiency., Methods: The study was a predefined secondary analysis of a randomized controlled trial enrolling 600 Nepalese infants aged 6 -11 mo, who were supplemented with 2 μg (2-3 recommended daily allowances) vitamin B 12 or placebo daily for 1 y. At the end of the study, LTL was measured in 497 participants. Mean LTL was compared between the treatment arms in the full sample and predefined subgroups based on markers of vitamin B 12 status, hemoglobin, sex, and growth indices., Results: LTL at end-study did not differ between the vitamin B 12 and placebo arm with a standardized mean difference (95% confidence interval) of 0.04 (-0.14, 0.21). There was no effect of vitamin B 12 on LTL in any of the subgroups., Conclusions: Providing daily vitamin B 12 for 1 y during infancy in a population at risk of vitamin B 12 deficiency does not affect LTL. This trial was registered at clinicaltrials.gov as NCT02272842., (Copyright © 2023 American Society for Nutrition. Published by Elsevier Inc. All rights reserved.)

Metformin is the most prescribed oral hypoglycemic drug and is considered by many health practitioners as the first-line treatment for non-insulin-dependent diabetes mellitus (T2DM). It is used either as a monotherapy or adjuvant to other anti-hyperglycemic agents. Most of its side effects are usually mild and self-limiting. However, several studies have shown an association between the use of metformin and low vitamin B 12 levels in diabetic patients. The current review aimed to provide a literature review of the current published reports on the association, the possible mechanisms, and the related individualized risk factors that might lead to this incidence. The most accepted mechanism of the effect of metformin on vitamin B 12 level is related to the absorption process where metformin antagonism of the calcium cation and interference with the calcium-dependent IF-vitamin B 12 complex binding to the ileal cubilin receptor. In addition, many risk factors have been associated with the impact of metformin on vitamin B 12 levels in diabetic patients such as dose and duration where longer durations showed a greater prevalence of developing vitamin B 12 deficiency. Male patients showed lower levels of vitamin B 12 compared to females. Black race showed a lower prevalence of vitamin B 12 deficiency in metformin-treated patients. Moreover, chronic diseases including T2DM, hyperlipidemia, coronary artery disease, polycystic ovary disease (PCOD), obesity, and metformin therapy were significantly associated with increased risk of vitamin B 12 deficiency., (© 2024. The Author(s).)

We report a case series of two patients who had similar skin pigmentation but were caused by vitamin B12 deficiency and Addison's disease. We further discuss the pathophysiology of skin hyperpigmentation in both of these disorders and the response to treatment. Our case report highlights the importance of the identification of simple bedside clinical signs to diagnose reversible causes of skin pigmentation., (© Journal of the Association of Physicians of India 2024.)

Purpose: To outline the prevalence of vitamin D and vitamin B 12 deficiencies in enuretic children., Methods: An analytical descriptive study was conducted on enuretic children who were followed up at the outpatient clinic for nocturnal enuresis at the Children's Hospital, Cairo University. Sociodemographic and clinical data were recorded. The levels of vitamin D and vitamin B 12 were assessed and correlated with the severity of enuresis., Results: Two hundred and eighty-eight children were enrolled. Insufficiency of Vitamin D predominated ( n  = 139; 48.3%). Vitamin D deficiency was present in 31.3%, n  = 90 and it was normal in 20.5%, n  = 59). Vitamin B 12 deficiency was observed in 25% of the studied children, n  = 72). The one-sample Wilcoxon signed-rank test was significant for both vitamins (P value =0.001). Vitamin D showed a stronger inverse correlation with the number of enuresis episodes per day than vitamin B 12 (-0.680 vs. -0.219 respectively). A cut-off of 13.7 ng/ml for vitamin D was detected, below which the child was predicted to have failed dry nights. Using multivariate logistic regression, higher vitamin D levels and behavioural treatment coexistence were significant protective factors for the absence of dry nights., Conclusion: Low levels of vitamin D and B 12 were detected in children with primary nocturnal enuresis, which could be considered a burden on the clinical severity of enuresis.

Pyridoxal 5'-phosphate (PLP), the catalytically active form of vitamin B 6 , acts as a cofactor in many metabolic processes. In humans, PLP is produced in the reactions catalysed by pyridox(am)ine 5'-phosphate oxidase (PNPO) and pyridoxal kinase (PDXK). Both PNPO and PDXK are involved in cancer progression of many tumours. The silencing of PNPO and PDXK encoding genes determines a strong reduction in tumour size and neoplastic cell invasiveness in models of acute myeloid leukaemia (in the case of PDXK) and ovarian and breast cancer (in the case of PNPO). In the present work, we demonstrate that pyridoxilidenerhodanine 5'-phosphate (PLP-R), a PLP analogue that has been tested by other authors on malignant cell lines reporting a reduction in proliferation, inhibits PNPO in vitro following a mixed competitive and allosteric mechanism. We also show that the unphosphorylated precursor of this inhibitor (PL-R), which has more favourable pharmacokinetic properties according to our predictions, is phosphorylated by PDXK and therefore transformed into PLP-R. On this ground, we propose the prototype of a novel prodrug-drug system as a useful starting point for the development of new, potential, antineoplastic agents., (© 2024 Federation of European Biochemical Societies.)

Background: Musculoskeletal disorders are an important cause of work absence. Clinical practice guidelines recommend nonsteroidal anti-inflammatory drugs (NSAIDs) for grade I-II cervical sprains. The combination of thiamine + pyridoxine + cyanocobalamin vitamins has been used, alone and in combination with NSAIDs, for pain and inflammation in musculoskeletal disorders., Objective: The objective of this study was to demonstrate the analgesic synergy of dexketoprofen, and the combination of vitamins thiamine + pyridoxine + cyanocobalamin in a fixed-dose combination (FDC) for the treatment of acute pain caused by grade I-II cervical sprains., Methods: We conducted a multicentre, prospective, randomized, double-blind, phase IIIb clinical study comparing two treatment groups: (1) dexketoprofen 25 mg/vitamin B (thiamine 100 mg, pyridoxine 50 mg and cyanocobalamin 0.50 mg) in an FDC (two or more active ingredients combined in a single dosage form) versus (2) dexketoprofen 25 mg monotherapy (single drug to treat a particular disease), one capsule or tablet orally, every 8 h for 7 days. Final mean, average change, and percentage change in pain perception (measured using a visual analogue scale [VAS]) were compared with baseline between groups. A p value < 0.05 was considered statistically significant. Analyses were conducted using SPSS software, v.29.0., Results: A statistically significant reduction in pain intensity was observed from the third day of treatment with the FDC compared with monotherapy (- 3.1 ± - 1.5 and - 2.6 ± - 1.1 cm, respectively) measured using the VAS (p = 0.011). Regarding the degree of disability, using the Northwick Park Neck Pain Questionnaire (NPQ), statistical difference was observed for the final measurement (7.5%, interquartile range [IQR] 2.5, 10.5; vs. 7.9%, IQR 5.0, 13.8; p = 0.028). A lower proportion of adverse events was reported when using the FDC., Conclusions: The FDC of dexketoprofen/thiamine + pyridoxine + cyanocobalamin vitamins demonstrated superior efficacy and a better safety profile compared with dexketoprofen monotherapy for pain treatment in patients with grade I-II cervical sprains., Clinical Trials Registration: NCT05001555, registered 29 July 2021 ( https://clinicaltrials.gov/study/NCT05001555 )., (© 2024. The Author(s).)

Recently, we have described the first supermolecular nanoentities of vitamin B 12 derivative, viz. monocyano form of heptabutyl cobyrinate, unique nanoparticles with strong noncovalent intermolecular interactions, emerging optical and catalytic properties. Their nearest analogue, heptamethyl cobyrinate (ACCby), exhibits bioactivity. Here, we demonstrate the first example of the formation of nanoparticles of this nucleotide-free analogue of vitamin B 12 in protein nanocarriers and neuroprotective activity in vivo of the own nanoform of the drug. The preparation and characterization of nanocarriers based on bovine serum albumin (BSA) loaded with vitamin B 12 (viz. cyano- and aquacobalamins) and ACCby were performed. Nucleotide-free analogue of vitamin B 12 is tightly retained by the protein structure and exists in an incorporated state in the form of nanoparticles. The effect of encapsulated drugs on the character and severity of primary generalized seizures in rats induced by the pharmacotoxicant thiosemicarbazide was studied. Cyanocobalamin and ACCby exhibited a neuroprotective effect. The best influence of the encapsulation on the effectiveness of the drugs was achieved in the case of AСCby, whose bioavailability as a neuroprotector did not change upon introduction in BSA particles, i.e., 33 % of surviving animals were observed upon ACCby administration in free form and in encapsulated state. No surviving rats were observed without the administration of drugs. Thus, BSA nanocarriers loaded by nanoparticles of nucleotide-free analogues of vitamin B 12, including hydrophobic ones, can be recommended for neuroprotection and targeted delivery., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Larissa A. Maiorova reports financial support was provided by Russian Science Foundation. Larissa A. Maiorova reports financial support was provided by Ministry of Science and Higher Education of the Russian Federation. Larissa A. Maiorova reports a relationship with Federal Research Center Computer Science and Control of Russian Academy of Sciences that includes: employment. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Vitamin B 12 is involved in many important biochemical reactions for humans, and its deficiency can lead to serious diseases. The industrial production of vitamin B 12 is achieved through microbial fermentation. In this work, we determine the crystal structures of the l-threonine-O-3-phosphate (Thr-P) decarboxylase CobC from Sinorhizobium meliloti (SmCobC), an industrial vitamin B 12 -producing bacterium, in apo form and in complex with a reaction intermediate. Our structures supported the Thr-P decarboxylase activity of SmCobC and revealed that the positively charged substrate-binding pocket between the large and small domains determines its substrate selectivity for Thr-P. Moreover, our results provided evidence for the proposition that the AP-P linker is formed by direct incorporation of AP-P in the biosynthetic pathway of vitamin B 12 in S.meliloti., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Traumatic brain injury is a highly irreversible process that consists of primary as well as secondary injury which develops and progresses over months to years, leading to cognitive dysfunctions. Vitamin B 12 received considerable interest due to its potential therapeutic properties. The pathways of vitamin B 12 are closely related to neuronal survival but its effects on the pathophysiology of injury with respect to cognition is a relatively unexplored area of research. In this study, we investigated, the effect of vitamin B 12 and its involvement in neuroprotection on TBI-induced pathophysiology in male Swiss albino mice. Our findings suggested that vitamin B 12 supplementation improves TBI-mediated neurological impairments, spatial and recognition memory, and anxiety-like behavior. Furthermore, the oxidative stress was reduced by declined homocysteine level with vitamin B 12 supplementation validating declined expression of astrocytes and TBI biomarkers. The studies on neuronal morphology revealed that vitamin B 12 supplementation increases the dendritic arborization and density of mushroom and filopodia-shaped spines and further increases the expression of synaptic plasticity-related genes and proteins. Taken together, our findings reveal that, supplementation of vitamin B 12 restored the TBI-induced downregulation of dendritic arborization, and spine density which ultimately increases synaptic plasticity, cell survival, and recovery of cognitive dysfunctions., Competing Interests: Declaration of competing interest The authors declare that there is no conflict of interest., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

The present study aimed to assess the potential effect of vitamin B 12 (Vit B 12 ) on cognition impairment caused by nicotine (Nic) cessation in adolescent male rats. Adolescent male rats were categorized into two main groups as vehicle (normal saline, intraperitoneally), and Nic group in which received Nic (2 mg/kg) from 21 to 42 days of ages and then the Nic group were divided into three groups as withdrawal (the animals returned to regular diet without treatment), second and third groups received bupropion (20 mg/kg), and Vit B 12 at three different doses including 0.5,1, and 1.5 mg/kg by oral gavage as treatments to attenuate Nic withdrawal symptoms. The last group including normal animals received the highest doses of Vit B 12 just in the Nic abstinence period to compare the effect of that with vehicle. In MWM, Vit B 12 and bupropion increased the time spent in the target quadrant that is strongly associated with spatial memory as well as the more time spent with the NORT. Vit B 12 and bupropion modulated both oxidant/antioxidant and inflammatory/anti-inflammatory balance, alongside inhibitory effect on AChE, and GFAP. However, BDNF and amyloid-B showed insignificant difference as compared to Vit B 12 and bupropion. Considering the present results and similar related studies, Vit B 12 can be introduced as a strong anti-oxidant, and anti-inflammatory agent by which probably improved memory impairment caused by Nic addiction accompanied by withdrawal. Further, other mechanisms including activity reduction of AChE, and GFAP should be considered; however, it needs further investigation and larger-scale evidences., Competing Interests: Declaration of Competing Interest There was no conflict of interest., (Copyright © 2024. Published by Elsevier B.V.)

Elevated homocysteine (Hcy) levels (≥15 μmol/L) in the elderly are frequently associated with a higher risk of cardiovascular disease and cognitive decline. Several studies have already shown an Hcy-lowering effect of B vitamin supplementation in cohorts deficient in these nutrients. The aim of this randomized, double-blinded 12-week intervention study was to investigate whether Hcy levels in healthy elderly subjects (75.4±4.5 years, n=133) could be lowered with a micronutrient supplement (i.e., 400 μg folic acid, 100 μg cobalamin). Difference in mean initial Hcy levels between intervention (17.6±7.1 μmol/L, n=65) and placebo group (18.9±6.1 μmol/L, n=68) was not significant. The prevalence of cobalamin and folate deficiency in the total study population was low: 27% had serum-cobalamin levels ≤150 pmol/L, 12% holo-transcobalamin (Holo-TC) levels ≤50 pmol/L, 13% low cobalamin status using the aggregated cobalamin marker 4cB12 and 10% red blood cell (RBC) folate ≤570 nmol/L. Nevertheless, the treated subjects still showed improved cobalamin and folate biostatus (serum cobalamin Δt 12 -t 0 : 63±48 pmol/L; Holo-TC Δt 12 -t 0 : 17±19 pmol/L; RBC folate Δt 12 -t 0 : 326±253 nmol/L) and Hcy levels (Δt 12 -t 0 : -3.6±5.7 μmol/L). The effects were statistically significant compared to the placebo group with p=0.005 (serum cobalamin), p=0.021 (Holo-TC), p=0.014 (RBC-folate) and p<0.001 (Hcy). The Hcy-lowering effect was dependent on the initial Hcy levels (p<0.001). Our findings suggest that elevated Hcy levels in elderly subjects can be lowered regardless of the initial cobalamin and folate biostatus.

Background: Chemical fortification and dose supplementation of vitamin B 12 are widely implemented to combat deficiency symptoms. However, in situ, fortification of vitamin B 12 in food matrixes can be a promising alternative to chemical fortification. The present study aimed to produce vitamin B 12 -rich, probiotic guava juice fermented with Levilactobacillus brevis strain KU15152. Pasteurized fresh guava juice was inoculated with 7.2 log CFU mL -1 L. brevis strain KU15152 and incubated for 72 h at 37 °C anaerobically. The antioxidants, total phenolic compounds, vitamin B 12 production, sugars, organic acids, pH and viable count were analyzed at 24, 48 and 72 h of incubation. The fermented juice was stored at 4 °C, and the changes in its functional properties were analyzed at 7-day intervals up to 28 days of storage., Results: During fermentation, the bacteria cell count was increased from 7.01 ± 0.06 to 9.76 ± 0.42 log CFU mL -1 after 72 h of fermentation and was decreased to 6.94 ± 0.34 CFU mL -1 during storage at 4 °C after 28 days. The pH, total soluble solids, crude fiber, citric acid and total sugars decreased, while titratable acidity, total protein, antioxidants, phenolic compounds and lactic acid contents increased during fermentation. The fermented guava juice exhibited higher 1,1-diphenyl-2-picrylhydrazyl (DPPH) and 2,2'-azino-bis-(3-ethylbenzothiazoline-6-sulfonic acid (ABTS)) radical scavenging activities (85.97% and 75.97%, respectively) at 48 h of fermentation. The concentration of active vitamin B 12 in the sample reached 109.5 μg L -1 at 72 h of fermentation. However, this concentration gradually decreased to 70.2 μg L -1 during the storage period. During storage for 28 days at 4 °C, both the fermented and control guava juices exhibited a decline in antioxidant and phenolic compound concentrations. Furthermore, the addition of 20% honey and guava flavor enhanced the organoleptic properties and acceptability of fermented guava juice., Conclusion: The value-added fermented guava juice could be a novel functional food product to combat vitamin B 12 deficiency. © 2024 The Author(s). Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry., (© 2024 The Author(s). Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.)

Background: Vitamin B 12 is a crucial B-group vitamin, first isolated from the liver due to its role in combating pernicious anemia. It is distinguished by its unique and complex structure, which makes its chemical synthesis challenging and expensive. Consequently, vitamin B 12 is alternatively obtained through microbial fermentations. Molasses, an affordable and safe agro-industrial waste, can be used as a carbon source for vitamin B 12 production, offering a cost-effective alternative to expensive sugars in the production medium., Results: A total of 87 yeast, actinomycete, and bacterial isolates were screened for vitamin B 12 production, with 15 isolates showing high productivity. Bacillus isolates were selected for further analysis using MALDI-TOF and molecular identification. These isolates were identified as four strains of Bacillus subtilis (MZ08, JT10, BY11, and JT17), one strains of Bacillus sp. (CB09), and one strain of Peribacillus acanthi (MZ01). Genetic circuits associated with vitamin B 12 production were demonstrated in a closely related strain of Peribacillus acanthi MZ01 strain. Three strains (MZ01, MZ08, and JT17) were selected for further evaluation of vitamin B 12 productivity under different sugar types (glucose, sucrose, fructose, lactose, and galactose) and varying inoculum sizes. The inoculum size significantly impacted vitamin B 12 production, with an increase from 5 to 10% enhancing yields. The ability of the strains to produce vitamin B 12 varied depending on the type of sugar used. Peribacillus acanthi MZ01 strain showed the highest productivity and subsequently, selected for optimizing vitamin B 12 production conditions using response surface methodology. Furthermore, the optimized conditions were then applied to molasses-based medium to achieve high vitamin B 12 yields by MZ01 strain., Conclusion: In this study, Peribacillus acanthi was characterized for the first time as a vitamin B 12 producer, demonstrating high productivity among various tested strains. The optimization of production conditions using response surface methodology, further enhanced vitamin B 12 yields, showcasing the strain's efficiency in microbial fermentations. This research also highlights the potential of using molasses as a cost-effective alternative carbon source, significantly reducing production costs., Competing Interests: Declarations Ethics approval and consent to participate Not applicable. Consent for publication Not applicable. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Although benzimidazoles are well-recognized compounds in medicinal chemistry, they occur in the natural world primarily as lower ligands of Vitamin B 12 and other cobamides. In this study, we present the synthesis of 5-methoxy-6-methylbenzimidazole and 5-hydroxy-6-methylbenzimidazole, and demonstrate their ability to produce functional cobamides and N-1'-α-glycosidic-benzimidazolyl-ribosylphosphate isomers which are putative B 12 biosynthesis intermediates.

Objective: To investigate the value of serum ferritin, folic acid and vitamin B 12 in the treatment of multiple myeloma (MM) with bortezomib combined with chemotherapy., Methods: Clinical data of 40 MM patients admitted to our hospital from January 2020 to August 2022 and 40 hematology outpatients during the same period were reviewed. All MM patients were treated with bortezomib combined with chemotherapy. The diagnostic efficacy of serum ferritin, folic acid and vitamin B 12 on MM was analyzed by ROC curve. The changes of serum ferritin, folic acid and vitamin B 12 in MM patients before and after treatment were compared. According to the mean values of serum ferritin, folic acid and vitamin B 12 , patients were divided into high and low expression groups, and the survival of patients between the groups was compared., Results: Before treatment, the levels of serum ferritin and vitamin B 12 in MM patients were significantly higher than those in control group, while folic acid was lower (all P <0.001). The area under the curve (AUC) of MM patients diagnosed with ferritin, folic acid and vitamin B 12 were 0.928, 0.843 and 0.867, the specificity was 100%, 67.50% and 72.50%, and the sensitivity was 80.00%, 95.00% and 87.50%, respectively. After 4 cycles of chemotherapy, there were 9 cases of complete remission (CR), 19 cases of very good partial remission (VGPR), 6 cases of PR, 4 cases of stable disease (SD) and 2 cases of progression disease (PD) in 40 MM patients. In CR group, ferritin and vitamin B 12 decreased but folic acid increased after treatment compared with before treatment (all P < 0.05). The overall survival (OS) rates of patients in low expression group of ferritin and vitamin B 12 were significantly higher than those in high expression group (both P < 0.01). The OS rate of patients in high expression group of folic acid was significantly higher than that in low expression group ( P < 0.01). Cox regression analysis showed that ferritin was an independent prognostic factor for MM patients ( HR =8.850, 95% CI : 2.267-34.553, P =0.002)., Conclusion: Serum ferritin, folic acid and vitamin B 12 have some auxiliary value in the diagnosis and efficacy evaluation of MM, and ferritin is an independent prognostic factor for MM.

Introduction: Identifying controllable risk factors for large-artery atherosclerosis (LAA) stroke is crucial due to its significant role as a leading cause of ischemic stroke. We aimed to validate the correlation of serum vitamin B 12 with LAA stroke., Methods: Inpatients with LAA stroke and healthy controls were retrospectively collected for a case-control study from January 2020 to May 2022. Serum vitamin B 12 concentration and other blood indicators, demographic, lifestyle factors and comorbidities were investigated. Logistic regression analysis was used to identify the correlation of serum vitamin B 12 concentrations with LAA stroke, meanwhile adjusted for confounding factors., Results: Patients with LAA stroke had significantly lower serum vitamin B 12 concentrations in comparison to those of controls. In the fully adjusted model, vitamin B 12 (per 1 interquartile range increase, odds ratio [OR] = 0.84, 95 % confidence interval [CI]: 0.77-0.91), vitamin B 12  < 200 pg/mL (OR=7.70, 95 %CI: 2.19-27.03) and vitamin B 12  < 300 pg/mL (OR=4.19, 95 %CI: 1.82-9.66) were independently factors for LAA stroke. Furthermore, the optimal cut-off values for vitamin B 12 to predict LAA stroke were 305.25 pg/mL (area under the curve [AUC] = 0.71) when unadjusted and 308.25 pg/mL when adjusted for age and sex (AUC=0.68). Lower vitamin B 12 concentrations were significantly associated with male sex, smoking, older age, higher neutrophil count, higher creatinine, lower folate and higher total homocysteine., Conclusion: Results indicate that low concentration of serum vitamin B 12 may be a strong predictor for the risk of LAA stroke., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.)

Vitamin B 12 , also known as cobalamin, is an essential organic cofactor for methionine synthase (METH), and is only synthesized by a subset of bacteria. Plants and fungi have an alternative methionine synthase (METE) that does not need B 12 and are typically considered not to utilize it. Some algae facultatively utilize B 12 because they encode both METE and METH, while other algae are dependent on B 12 as they encode METH only. We performed phylogenomic analyses of METE, METH and 11 further proteins involved in B 12 metabolism across more than 1600 plant and algal genomes and transcriptomes (e.g. from OneKp), demonstrating the presence of B 12 -associated metabolism deep into the streptophytes. METH and five further accessory proteins (MTRR, CblB, CblC, CblD and CblJ) were detected in the hornworts (Anthocerotophyta), and two (CblB and CblJ) were identified in liverworts (Marchantiophyta) in the bryophytes, suggesting a retention of B 12 -metabolism in the last common land plant ancestor. Our data further show more limited distributions for other B 12 -related proteins (MCM and RNR-II) and B 12 dependency in several algal orders. Finally, considering the collection sites of algae that have lost B 12 metabolism, we propose freshwater-to-land transitions and symbiotic associations to have been constraining factors for B 12 availability in early plant evolution. This article is part of the theme issue 'The evolution of plant metabolism'.

Previous studies have shown that B vitamins can relieve migraine. However, the association between vitamin B 6 and folate, 2 important B vitamins consumed in the diet, with migraine have received minimal attention. This study explored the independent relationships between dietary vitamin B 6 and folate intake with migraine and the interaction effect of these 2 nutrients on migraine in US adults. We hypothesized that vitamin B 6 and folate intake would be inversely associated with migraine. This study included cross-sectional data from participants aged 20 years and older who participated in the National Health and Nutrition Examination Survey from 1999 to 2004. We conducted multivariate logistic regression and restricted cubic spline regression to explore the association between dietary vitamin B 6 and folate intake on migraine. Also, relative excess risk due to interaction, attributable proportion of interaction, and synergy index were used to assess additive interactions. A total of 7017 participants were included in this study, 1350 of whom were migraineurs. We determined that vitamin B 6 and folate intake revealed a negative association with severe headache or migraine (0.66; 95% confidence interval [CI], 0.47-0.89; P = .01 and 0.57; 95% CI, 0.42-0.78; P = .002]), respectively. Also, a significant interaction effect between a high mass of vitamin B 6 and folate intake was observed for a lower risk of migraine (relative excess risk due to interaction, 0.28 [95% CI, 0.05-0.51]; attributable proportion of interaction: 0.45 [95% CI, 0.05-0.86]; synergy index: 0.58 [95% CI, 0.40-0.83]). A high mass of vitamin B 6 and folate intake (vitamin B 6 intake ≥ 2.39 mg/day and folate intake ≥ 502.01 µg/day) presented a synergistic interaction with migraine, suggesting that these 2 nutrients might be beneficial in preventing migraine., Competing Interests: Author Declarations None., (Copyright © 2023 Elsevier Inc. All rights reserved.)

The analysis of vitamin B 12 in infant formulas typically requires the use of cyanide during sample preparation to convert the unstable vitamers (hydroxocobalamin, methylcobalamin and adenosylcobalamin) to cyanocobalamin, the most stable form of vitamin B 12 . To eliminate the risk to laboratory analysts in handling cyanide, alternative strategies are preferred for the analysis of vitamin B 12 . This research demonstrates the use of cobalamin-derived α-ribazole (a nucleoside moiety of vitamin B 12 ) to determine total vitamin B 12 content. Infant formula samples underwent protein denaturation and sugar removal with subsequent acidic hydrolysis and dephosphorylation employed to release α-ribazole, which was isolated by boronate affinity chromatography then analysed by hydrophilic interaction liquid chromatography with fluorescence detection. The method was validated using bovine- and ovine milk-based infant formula samples. The newly developed method was linear over the range of 0.65-6.48 ng mL -1 with repeatability of 3.78-5.47% relative standard deviation (RSD r , n = 10) and an intermediate precision of 3.59-10.0% RSD iR (n = 10). The limits of detection and quantitation (LOD and LOQ) were 0.4 and 1.2 μg 100 g -1 of dry weight, respectively. Accuracy was 68.9-76.4% and 68.7-80.0% at 50 and 150% of typical B 12 concentrations in infant formula, respectively. The validated method was applied to eleven infant formulas and no statistical difference (p = 0.45, α = 0.05) was found when comparing with the results obtained using the AOAC Official Method 2014.02 high performance liquid chromatography with ultraviolet detection that requires the use of cyanide. These results indicate that the newly validated method is not only reliable but also offers a safer alternative for routine vitamin B 12 determination in infant formula while maintaining high accuracy and precision., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Objectives: The relationship between food allergies and vitamin B 12 deficiency in young children remains unclear despite extensive studies on the nutritional status of affected children. The aim of this study was to compare vitamin B 12 levels in children with recently diagnosed food allergies and healthy children ages 0 to 36 mo., Methods: A retrospective study at Başkent University Hospital analyzed 773 patients ages 0 to 36 mo. Participants were divided into two groups: food allergy and healthy. Vitamin B 12 deficiency (<300 ng/mL) was assessed using χ 2 tests and regression analyses., Results: The sample comprised 773 children ages 0 to 36 mo, with a mean age of 16 ± 9 mo (range: 1-36). Among the participants, 399 (52%) were healthy children, whereas 374 (48%) had food allergies. The prevalence of vitamin B 12 deficiency was higher in children with food allergies (38%) than in healthy children (21%; P < 0.001). According to both univariate and multivariate regression analyses, formula feeding showed a negative association with vitamin B 12 deficiency (β = -0.54; 95% confidence interval [CI], 0.35-0.97; P = 0.038). On the other hand, having allergic diseases (β = 0.69; 95% CI, 0.30-0.83; P = 0.040) and breastfeeding for <6 mo (β = 1.35; 95% CI, 1.41-10.50-0.50; P = 0.009) exhibited a positive association with vitamin B 12 deficiency., Conclusion: Food-allergic children ages 0 to 36 mo were at higher risk for vitamin B 12 deficiency. Formula feeding had a protective effect, whereas allergic diseases and breastfeeding for <6 mo were risk factors. Further investigation is needed to understand the underlying mechanisms. Monitoring B 12 levels and interventions are crucial for the nutritional well-being of food-allergic children., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objectives : Vitamin B complexes are frequently used in clinical practice for peripheral nerve trauma. However, there is a lack of scientific data on their effectiveness. This study aims to investigate the impact of the vitamin B complex on nerve recovery in a rat model of peripheral nerve paralysis. Materials and Methods : Sixty male Wistar Albino rats were divided into six groups. Models of nerve injury, including blunt trauma, nerve incision, and autograft, were performed on all rats approximately 1 cm distal to the sciatic notch. B-complex vitamins were injected intraperitoneally at 0.2 mL/day to the treatment groups. The control groups were given 0.2 mL/day saline. After 1 month, the study was terminated, electromyography (EMG) was performed to measure the conduction velocity, and nerve tissue was taken from the repair line. The sciatic function indexes (SFIs) were calculated and analyzed. The histopathological samples were stained with hematoxylin and eosin and Toluidine blue and examined with a light microscope. Pathologically, myelination, fibrosis, edema, and mast cell densities in the nervous tissue were evaluated. Results : The vitamin B treatment groups demonstrated significant improvements in SFI compared to the control groups, indicating functional improvement in nerve damage ( p < 0.05). In the nerve graft group, the vitamin B group showed a shorter latency, higher velocity, and larger peak-to-peak compared to the controls ( p < 0.05). In the nerve transection group, the vitamin B group had better latency, velocity, and peak-to-peak values than the controls ( p < 0.05). In the crush injury group, the vitamin B group exhibited an improved latency, velocity, and peak-to-peak compared to the controls ( p < 0.05). Better myelination, less fibrosis, edema, and mast cells were also in the vitamin B group ( p < 0.05). Conclusions : Vitamin B treatment significantly improves nerve healing and function in peripheral nerve injuries. It enhances nerve conduction, reduces fibrosis, and promotes myelination, indicating its therapeutic potential in nerve regeneration.

Background: Folic acid and vitamin B 12 (FV), being B vitamins, not only facilitate the remethylation of homocysteine (Hcy) but also contribute to embryonic development. This study aimed to assess the impact of FV supplementation during late pregnancy on sows' reproductive performance, amino acid metabolism, placental angiogenesis, and related parameters. Twenty primiparous sows at day 60 of gestation were randomly allocated to two groups: a basal diet (CON) group and a group receiving a basal diet supplemented with folic acid at 20 ppm and vitamin B 12 at 125 ppb., Results: The findings revealed that dietary FV supplementation significantly reduced the incidence of intrauterine growth retardation compared to the CON group (P < 0.05). Furthermore, it led to a decrease in the Hcy levels in umbilical cord serum (P < 0.05) and activation of the placental mechanistic target of rapamycin complex 1 (mTORC1) signaling pathway (P < 0.05). Additionally, FV supplementation lowered placental malondialdehyde levels (P < 0.05) and increased the expression of placental thioredoxin (P = 0.05). Moreover, maternal FV supplementation notably elevated placental vascular density (P < 0.05) and the expression of sodium-coupled neutral amino acid transporter 2 (SNAT2) (P < 0.05), as well as amino acid concentrations in umbilical cord blood (P < 0.05)., Conclusion: Maternal FV supplementation during medium to late gestation reduced Hcy levels in umbilical cord blood and positively impacted fetal development. This improvement was closely associated with increased placental antioxidant capacity and vascular density, as well as activation of the placental mTORC1-SNAT2 signaling pathway. © 2023 Society of Chemical Industry., (© 2023 Society of Chemical Industry.)

Objective: The associations between plasma vitamin B 12 level and anemia under different dietary patterns in elderly Chinese people are poorly understood. We aimed to examine the associations between plasma vitamin B 12 levels and anemia under different dietary patterns in adults aged 65 years and older in nine longevity areas in China., Methods: A total of 2405 older adults completed a food frequency questionnaire at the same time as a face-to-face interview. The dietary diversity score (DDS) was assessed based on the food frequency questionnaire, with the low DDS group referring to participants with a DDS score ≤ 4 points. Vitamin B 12 levels were divided into two groups of high (>295 pg/mL) and low (≤ 295 pg/mL) with the median used as the cut-off point. Sub-analyses were also performed on older adults divided into tertiles of vitamin B 12 levels: low (< 277 pg/mL), medium (277-375 pg/mL) and high (> 375 pg/mL) to study the association of these levels with anemia., Results: Six hundred ninety-five (28.89%) of these people were diagnosed with anemia and had a mean age of 89.3 years. Higher vitamin B 12 levels were associated with a decreased risk of anemia (multi-adjusted OR, 0.59, [95% CI, 0.45 ~ 0.77] P < 0.001) in older adults with a low DDS, whereas no significant association between vitamin B 12 levels and anemia was found in older adults with a high DDS in a full-model after adjustment for various confounding factors (multi-adjusted OR, 0.88, [95% CI, 0.65 ~ 1.19], P = 0.41)., Conclusion: The relationship between vitamin B 12 levels and the prevalence of anemia was significant only when the level of dietary diversity in the older adults was relatively low. The dietary structure of the population should be taken into consideration in combination in order to effectively improve anemia status by supplementing vitamin B 12 ., (© 2024. The Author(s).)

Deficiency of vitamin B 12 (B 12 or cobalamin), an essential water-soluble vitamin, leads to neurological damage, which can be irreversible and anaemia, and is sometimes associated with chronic disorders such as osteoporosis and cardiovascular diseases. Clinical tests to detect B 12 deficiency lack specificity and sensitivity. Delays in detecting B 12 deficiency pose a major threat because the progressive decline in organ functions may go unnoticed until the damage is advanced or irreversible. Here, using targeted unbiased metabolomic profiling in the sera of subjects with low B 12 levels v control individuals, we set out to identify biomarker(s) of B 12 insufficiency. Metabolomic profiling identified seventy-seven metabolites, and partial least squares discriminant analysis and hierarchical clustering analysis showed a differential abundance of taurine, xanthine, hypoxanthine, chenodeoxycholic acid, neopterin and glycocholic acid in subjects with low B 12 levels. Random forest multivariate analysis identified a taurine/chenodeoxycholic acid ratio, with an AUC score of 1, to be the best biomarker to predict low B 12 levels. Mechanistic studies using a mouse model of B 12 deficiency showed that B 12 deficiency reshaped the transcriptomic and metabolomic landscape of the cell, identifying a downregulation of methionine, taurine, urea cycle and nucleotide metabolism and an upregulation of Krebs cycle. Thus, we propose taurine/chenodeoxycholic acid ratio in serum as a potential biomarker of low B 12 levels in humans and elucidate using a mouse model of cellular metabolic pathways regulated by B 12 deficiency.

The recent investigation targets to use adapted carbon paste (CP) with copper nanoparticles (CuNs) operating in a phosphate buffer (PBS) medium with a pH range of 5.0-8.0, to synthesize a novel, susceptible, and simple electrochemical sensor for the detection of one of the most important drugs, vitamin B 6 . Copper (Cu) is one of the most three common essential trace elements found in the bodies of both humans and animals, along with iron and zinc for all crucial physiological and biochemical functions. Its properties, which are assessed using a variety of methods including scanning electron microscopy (SEM), cyclic voltammetry (CV), differential pulse voltammetry (DPV), and electrochemical impedance spectroscopy (EIS), have also drawn a lot of attention recently. We considered the effects of pH, buffer, scan rate, interference, and calibration curve. The susceptible electrode's linear calibration curve encompassed concentration values between 8.88 and 1000.0 µM. The calculated limits of detection and quantification were 32.12 and 107.0 µM, respectively. Furthermore, this method was established in real human urine samples and drug validation which have been shown satisfactory results for vitamin B 6 detection., (© 2024. The Author(s).)

Arthrospira (Limnospira) maxima (A. maxima) and Chlorella vulgaris (Ch. vulgaris) are among the approved microalgae and cyanobacteria (MaC) in the food industry that are known to be safe for consumption. However, both organisms are controversial regarding their vitamin B 12 content, due to the possible occurrence of pseudo-cobalamin. Concurrently, their nutrition profiles remain understudied. The main purpose of the present study was to identify their nutrition profiles, focusing mainly on vitamin B 12 , amino acids, and micronutrients under iron-induced hormesis (10 mg/L Fe in treated samples). Our findings indicate a higher B 12 content in A. maxima compared to Ch. vulgaris (both control and treated samples). Using liquid chromatography with tandem mass spectrometry (LC-MS/MS), the cyanocobalamin content was determined as 0.42 ± 0.09 μg/g dried weight (DW) in the A. maxima control and 0.55 ± 0.02 μg/g DW in treated A. maxima, resulting in an insignificant difference. In addition, the iron-enriched medium increased the amount of iron in both tested biomasses (p < 0.01). However, a more pronounced (approximately 100×) boost was observed in Ch. vulgaris, indicating a better absorption capacity (control Ch. vulgaris 0.16 ± 0.01 mg/g Fe, treated Ch. vulgaris 15.40 ± 0.34 mg/g Fe). Additionally, Ch. vulgaris also showed a higher micronutrient content. Using both tested microalgae, meeting the sufficient recommended daily mineral allowance for an adult is possible. By combining biomass from A. maxima and Ch. vulgaris in a ratio of 6:1, we can fulfill the recommended daily allowance of vitamin B 12 and iron by consuming 6 tablets/6 g. Importantly, iron hormesis stimulated amino acid composition in both organisms. The profile of amino acids may suggest these biomasses as promising potential nutrition sources., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

Background: Vitamin B 12 and folate are essential micronutrients, a deficiency of which causes anaemia, poor growth and an increased risk of infections, along with irreversible neurological damage to the developing brain in children., Methods: A hospital-based prospective observational study was conducted in 100 children with severe acute malnutrition (SAM) aged 6-59 months admitted to a tertiary-care facility in northern India from July 2021 to June 2022. A structured proforma was used to record socio-demographic information, a detailed clinical history, results of general and systemic physical examination and a detailed anthropometric assessment. Serum folate and vitamin B 12 were estimated by electrochemiluminescence., Results: The mean age of the children was 24.18 months, and 64.0% were aged 6-12 months. The male-to-female ratio was 1.08:1. Anaemia was present in 87.0% of the children, and it was severe in 35% of them. There was serum vitamin B 12 and folate deficiency in 61.0% and 19.0%, respectively. A deficiency of vitamin B 12 was significantly associated with delayed developmental milestones in all domains, a mid-upper-arm circumference of <11.5 cm, severe anaemia, a low platelet count and folate deficiency, and a folate deficiency was significantly associated with older age, delayed developmental milestones in all domains, severe anaemia, a low platelet count and vitamin B 12 deficiency., Conclusion: Vitamin B 12 deficiency is highly prevalent in children aged 6-59 months with SAM, but the prevalence of folate deficiency is much lower. Apart from iron and folic acid supplementation, government programmes should consider vitamin B 12 supplementation for children aged 6-59 months.

Propionic acid links the oxidation of branched-chain amino acids and odd-chain fatty acids to the TCA cycle. Gut microbes ferment complex fiber remnants, generating high concentrations of short chain fatty acids, acetate, propionate and butyrate, which are shared with the host as fuel sources. Analysis of vitamin B 12 -dependent propionate utilization in skin biopsy samples has been used to characterize and diagnose underlying inborn errors of cobalamin (or B 12 ) metabolism. In these cells, the B 12 -dependent enzyme, methylmalonyl-CoA mutase (MMUT), plays a central role in funneling propionate to the TCA cycle intermediate, succinate. Our understanding of the fate of propionate in other cell types, specifically, the involvement of the β-oxidation-like and methylcitrate pathways, is limited. In this study, we have used [ 14 C]-propionate tracing in combination with genetic ablation or inhibition of MMUT, to reveal the differential utilization of the B 12 -dependent and independent pathways for propionate metabolism in fibroblast versus colon cell lines. We demonstrate that itaconate can be used as a tool to investigate MMUT-dependent propionate metabolism in cultured cell lines. While MMUT gates the entry of propionate carbons into the TCA cycle in fibroblasts, colon-derived cell lines exhibit a quantitatively significant or exclusive reliance on the β-oxidation-like pathway. Lipidomics and metabolomics analyses reveal that propionate elicits pleiotropic changes, including an increase in odd-chain glycerophospholipids, and perturbations in the purine nucleotide cycle and arginine/nitric oxide metabolism. The metabolic rationale and the regulatory mechanisms underlying the differential reliance on propionate utilization pathways at a cellular, and possibly tissue level, warrant further elucidation., Competing Interests: Conflict of interest The authors declare that they have no conflicts of interest with the contents of this article., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Infertility impacts 16% of North American couples, with male factor infertility contributing to ∼30% of cases. Reproductive hormones, especially testosterone, are essential for spermatogenesis. An age-independent population-level decline in testosterone concentrations over the past few decades has been proposed to be a consequence of diet and lifestyle changes. Vitamin B 12 is present in the testes and has been suggested as an adjuvant nutritional therapy for male infertility due to its potential to improve sperm parameters. However, evidence examining the relationship between vitamin B 12 and reproductive hormones is limited., Objectives: The objective was to cross-sectionally examine the relationship between serum vitamin B 12 and male reproductive hormones (luteinizing hormone, follicular stimulating hormone, total testosterone, estradiol, and prolactin)., Methods: Men with infertility (n = 303) were recruited from Mount Sinai Hospital in Toronto, Canada. Serum was analyzed for vitamin B 12 and reproductive hormones. Statistical analyses included nonparametric Spearman's rank correlation coefficient, linear regression, logistic regression, and effect modification by age and BMI linear regressions., Results: An independent monotonic relationship between serum vitamin B 12 and total testosterone (ρ = 0.19, P = 0.001) was observed. Serum vitamin B 12 was linearly associated with total testosterone (unadjusted β = 0.0007, P = 0.008 and adjusted β = 0.0005, P = 0.03). Compared to individuals in the lowest tertile of serum vitamin B 12 , those in the middle tertile (adjusted odds ratio [OR] = 0.48; 95% confidence interval [CI]: 0.25, 0.93, P = 0.03) and the highest tertile (unadjusted OR = 0.41; 95% CI: 0.22, 0.77, P = 0.005 and adjusted OR = 0.44; 95% CI: 0.22, 0.87, P = 0.02) had reduced odds of testosterone deficiency., Conclusions: These findings suggest that among men with infertility, low serum vitamin B 12 is associated with a higher risk of testosterone deficiency and impaired androgenic hormonal profiles that impact spermatogenesis and consequently, fertility., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

The Burkholderia cepacia complex (Bcc) consists of opportunistic pathogens known to cause pneumonia in immunocompromised individuals, especially those with cystic fibrosis. Treating Bcc pneumonia is challenging due to the pathogens' high multidrug resistance. Therefore, inhalation therapy with tobramycin powder, which can achieve high antibiotic concentrations in the lungs, is a promising treatment option. In this study, we investigated potential mechanisms that could compromise the effectiveness of tobramycin therapy. By selecting for B. cenocepacia survivors against tobramycin, we identified three spontaneous mutations that disrupt a gene encoding a key enzyme in the biosynthesis of cobalamin (Vitamin B 12 ). This disruption may affect the production of succinyl-CoA by methylmalonyl-CoA mutase, which requires adenosylcobalamin as a cofactor. The depletion of cellular succinyl-CoA may impact the tricarboxylic acid (TCA) cycle, which becomes metabolically overloaded upon exposure to tobramycin. Consequently, the mutants exhibited significantly reduced reactive oxygen species (ROS) production. Both the wild-type and mutants showed tolerance to tobramycin and various other bactericidal antibiotics under microaerobic conditions. This suggests that compromised ROS-mediated killing, due to the impacted TCA cycle, underlies the mutants' tolerance to bactericidal antibiotics. The importance of ROS-mediated killing and the potential emergence of mutants that evade it through the depletion of cobalamin (Vitamin B 12 ) provide valuable insights for developing strategies to enhance antibiotic treatments of Bcc pneumonia.

Aim: Vitamin B 12 deficiency is common in the elderly population. Standard treatment via intramuscular injections, however, has several disadvantages. Safer and more convenient dosage forms such as intranasal are therefore being explored. This study compares the effects of two intranasal vitamin B 12 dosage regimens in elderly vitamin B 12 -deficient patients., Methods: Sixty patients ≥65 years were randomly assigned to either a loading dose (daily administration for 14 days followed by weekly administration) or a no loading dose (administration every 3 days) regimen for 90 days. Each dose contained 1000 μg cobalamin. Total vitamin B 12 , holotranscoblamin (holoTC), methylmalonic acid (MMA) and total homocysteine (tHcy) levels in serum were measured on days 0, 7, 14, 30, 60 and 90., Results: Both dosage regimens resulted in a rapid increase of vitamin B 12 and holoTC concentrations and normalization of initial high, MMA and tHcy concentrations. The loading dose regimen resulted in the fastest and greatest increase to a median vitamin B 12 of 1090 pmol/L (reference 350-650 pmol/L) concentration after 14 days. Following weekly administration, B 12 rapidly decreased to a median concentration of 530 pmol/L after 90 days. The no loading dose regimen resulted in a steady increase to a median vitamin B 12 of 717 pmol/L after 90 days., Conclusions: Intranasal vitamin B 12 administration is an effective and suitable way to replenish and sustain vitamin B 12 levels in elderly patients., (© 2024 The Authors. British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.)

The aim of this study was to investigate the behavior interaction of α-Casein-B 12 and β-Casein-B 12 complexes as binary systems through the methods of multiple spectroscopic, zeta potential, calorimetric, and molecular dynamics (MD) simulation. Fluorescence spectroscopy denoted the role ofB 12 as a quencher in both cases of α-Casein and β-Casein fluorescence intensities, which also verifies the existence of interactions. The quenching constants of α-Casein-B 12 and β-Casein-B 12 complexes at 298 K in the first set of binding sites were 2.89 × 10 4 and 4.41 × 10 4 M -1 , while the constants of second set of binding sites were 8.56 × 10 4 and 1.58 × 10 5 M -1 , respectively. The data of synchronized fluorescence spectroscopy at Δλ = 60 nm were indicative of the closer location of β-Casein-B 12 complex to the Tyr residues. Additionally, the binding distance between B 12 and the Trp residues of α-Casein and β-Casein were obtained in accordance to the Förster's theory of nonradioactive energy transfer to be 1.95 nm and 1.85 nm, respectively. Relatively, the RLS results demonstrated the production of larger particles in both systems, while the outcomes of zeta potential confirmed the formation of α-Casein-B 12 and β-Casein-B 12 complexes and approved the existence of electrostatic interactions. We also evaluated the thermodynamic parameters by considering the fluorescence data at three varying temperatures. According to the nonlinear Stern-Volmer plots of α-Casein and β-Casein in the presence of B 12 in binary systems, the two sets of binding sites indicated the detection of two types of interaction behaviors. Time-resolved fluorescence results revealed that the fluorescence quenching of complexes are static mechanism. Furthermore, the outcomes of circular dichroism (CD) represented the occurrence of conformational changes in α-Casein and β-Casein upon their binding to B 12 as the binary system. The experimental results that were obtained throughout the binding of α-Casein-B 12 and β-Casein-B 12 complexes were confirmed by molecular modeling.Communicated by Ramaswamy H. Sarma.

The water-soluble vitamin, vitamin B 12 , also known as cobalamin, plays a crucial role in cellular metabolism, particularly in DNA synthesis, methylation, and mitochondrial functionality. Its deficiency can lead to hematological and neurological disorders; however, the manifestation of these clinical outcomes is relatively late. It leads to difficulties in the early diagnosis of vitamin B 12 deficiency. A prolonged lack of vitamin B 12 may have severe consequences including increased morbidity to neurological and cardiovascular diseases. Beyond inadequate dietary intake, vitamin B 12 deficiency might be caused by insufficient bioavailability, blood transport disruptions, or impaired cellular uptake and metabolism. Despite nearly 70 years of knowledge since the isolation and characterization of this vitamin, there are still gaps in understanding its metabolic pathways. Thus, this review aims to compile current knowledge about the crucial proteins necessary to efficiently accumulate and process vitamin B 12 in humans, presenting these systems as a multi-protein network. The epidemiological consequences, diagnosis, and treatment of vitamin B 12 deficiency are also highlighted. We also discuss clinical warnings of vitamin B 12 deficiency based on the ongoing test of specific moonlighting proteins engaged in vitamin B 12 metabolic pathways.

Whether the long-term treatment of patients with proton pump inhibitors (PPIs) with different diseases [GERD, Zollinger-Ellison syndrome (ZES), etc.] can result in vitamin B 12 (VB 12 ) deficiency is controversial. In this study, in 175 patients undergoing long-term ZES treatment with anti-acid therapies, drug-induced control acid secretory rates were correlated with the presence/absence of VB 12 deficiency, determined by assessing serum VB 12 levels, measurements of VB 12 body stores (blood methylmalonic acid (MMA) and total homocysteine[tHYC]), and other features of ZES. After a mean of 10.2 yrs. of any acid treatment (5.6 yrs. with PPIs), 21% had VB 12 deficiency with significantly lower serum and body VB 12 levels ( p < 0.0001). The presence of VB 12 deficiency did not correlate with any feature of ZES but was associated with a 12-fold lower acid control rate, a 2-fold higher acid control pH (6.4 vs. 3.7), and acid control secretory rates below those required for the activation of pepsin (pH > 3.5). Over a 5-yr period, the patients with VB 12 deficiency had a higher rate of achlorhydria (73% vs. 24%) and a lower rate of normal acid secretion (0% vs. 49%). In conclusion, in ZES patients, chronic long-term PPI treatment results in marked acid hyposecretion, resulting in decreased serum VB 12 levels and decreased VB 12 -body stores, which can result in VB 12 deficiency.

Carbon and chlorine isotope effects for biotransformation of chloroform by different microbes show significant variability. Reductive dehalogenases (RDase) enzymes contain different cobamides, affecting substrate preferences, growth yields, and dechlorination rates and extent. We investigate the role of cobamide type on carbon and chlorine isotopic signals observed during reductive dechlorination of chloroform by the RDase CfrA. Microcosm experiments with two subcultures of a Dehalobacter-containing culture expressing CfrA-one with exogenous cobamide (Vitamin B 12 , B12 + ) and one without (to drive native cobamide production)-resulted in a markedly smaller carbon isotope enrichment factor (ε C, bulk ) for B12 - (-22.1 ± 1.9‰) compared to B12 + (-26.8 ± 3.2‰). Both cultures exhibited significant chlorine isotope fractionation, and although a lower ε Cl, bulk was observed for B12 - (-6.17 ± 0.72‰) compared to B12 + (-6.86 ± 0.77‰) cultures, these values are not statistically different. Importantly, dual-isotope plots produced identical slopes of Λ Cl/C (Λ Cl/C, B12+  = 3.41 ± 0.15, Λ Cl/C, B12 - = 3.39 ± 0.15), suggesting the same reaction mechanism is involved in both experiments, independent of the lower cobamide bases. A nonisotopically fractionating masking effect may explain the smaller fractionations observed for the B12 - containing culture., (© 2024 The Author(s). MicrobiologyOpen published by John Wiley & Sons Ltd.)

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 B 12 (B 12 ). Because B 12 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 B 12 supplement. Studies determining the dose and frequency of B 12 to be taken by healthy individuals on a plant-based diet to support an adequate B 12 status are scarce. Here, we summarize the natural sources, metabolic requirements, biomarker findings with and without supplementation with B 12 , and current recommendations to help prevent vitamin B 12 deficiency in healthy individuals adhering or transitioning to plant-based diets. This review focuses on the prevention of vitamin B 12 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 B 12 resulting from pernicious anemia due to atrophic gastritis, other acquired causes of B 12 malabsorption or to those with genetic disorders that impair vitamin B 12 absorption, transport and utilization., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Cobalamin (vitamin B 12 , herein referred to as B 12 ) is an essential cofactor for most marine prokaryotes and eukaryotes 1,2 . Synthesized by a limited number of prokaryotes, its scarcity affects microbial interactions and community dynamics 2-4 . Here we show that two bacterial B 12 auxotrophs can salvage different B 12 building blocks and cooperate to synthesize B 12 . A Colwellia sp. synthesizes and releases the activated lower ligand α-ribazole, which is used by another B 12 auxotroph, a Roseovarius sp., to produce the corrin ring and synthesize B 12 . Release of B 12 by Roseovarius sp. happens only in co-culture with Colwellia sp. and only coincidently with the induction of a prophage encoded in Roseovarius sp. Subsequent growth of Colwellia sp. in these conditions may be due to the provision of B 12 by lysed cells of Roseovarius sp. Further evidence is required to support a causative role for prophage induction in the release of B 12 . These complex microbial interactions of ligand cross-feeding and joint B 12 biosynthesis seem to be widespread in marine pelagic ecosystems. In the western and northern tropical Atlantic Ocean, bacteria predicted to be capable of salvaging cobinamide and synthesizing only the activated lower ligand outnumber B 12 producers. These findings add new players to our understanding of B 12 supply to auxotrophic microorganisms in the ocean and possibly in other ecosystems., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Background: Vitamin B inadequacies and elevated homocysteine status have been associated with impaired cognitive and cardiometabolic health with aging. There is, however, a scarcity of research investigating integrated profiles of one-carbon (1C) metabolites in this context, including metabolites of interconnected folate, methionine, choline oxidation, and transsulfuration pathways., Objectives: The study aimed to examine associations between vitamins B and 1C metabolites with cardiometabolic health and cognitive function in healthy older adults, including the interactive effects of Apolipoprotein E-ε4 status., Methods: Three hundred and thirteen healthy participants (65-74 y, 65% female) were analyzed. Vitamins B were estimated according to dietary intake (4-d food records) and biochemical status (serum folate and vitamin B 12 ). Fasting plasma 1C metabolites were quantified by liquid chromatography with tandem mass spectrometry. Measures of cardiometabolic health included biochemical (lipid panel, blood glucose) and anthropometric markers. Cognitive function was assessed by the Computerized Mental Performance Assessment System (COMPASS) and Montreal Cognitive Assessment (MoCA). Associations were analyzed using multivariate linear (COMPASS, cardiometabolic health) and Poisson (MoCA) regression modeling., Results: Over 90% of participants met dietary recommendations for riboflavin and vitamins B 6 and B 12 , but only 78% of males and 67% of females achieved adequate folate intakes. Higher serum folate and plasma betaine and glycine concentrations were associated with favorable cardiometabolic markers, whereas higher plasma choline and homocysteine concentrations were associated with greater cardiometabolic risk based on body mass index and serum lipids concentration values (P< 0.05). Vitamins B and homocysteine were not associated with cognitive performance in this cohort, though higher glycine concentrations were associated with better global cognitive performance (P = 0.017), episodic memory (P = 0.016), and spatial memory (P = 0.027) scores. Apolipoprotein E-ε4 status did not modify the relationship between vitamins B or 1C metabolites with cognitive function in linear regression analyses., Conclusions: Vitamin B and 1C metabolite profiles showed divergent associations with cardiometabolic risk markers and limited associations with cognitive performance in this cohort of healthy older adults., Competing Interests: Conflict of interest The authors declare they have no conflict of interest., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)