Homocysteine, vitamin B12, and folate circulating levels in women with and without polycystic ovary syndrome: A systematic review and meta-analysis.

BACKGROUND: Some studies have reported that homocysteine, vitamin B12, and folic acid levels are associated with polycystic ovary syndrome (PCOS), whereas other studies yielded controversial results. OBJECTIVES: This study aimed to systematize the available evidence of homocysteine, vitamin B12, and folate levels in women with and without PCOS. DESIGN: Systematic review and meta-analysis. DATA SOURCES AND METHODS: A systematic search without language restrictions was performed on PubMed, Ovid/Medline, Scopus, Embase, and Web of Science. In addition, the reference lists of the selected studies were reviewed. The Newcastle-Ottawa Scale was employed to evaluate the quality of studies. The means and standard deviations of the outcomes were pooled as standardized mean differences (SMDs) with 95% confidence intervals (CI). Furthermore, the DerSimonian and Laird method was employed for the quantitative synthesis. RESULTS: A total of 75 studies met the eligibility criteria for at least one outcome. Patients with PCOS had higher circulating homocysteine levels than those without (SMD: 0.82; 95% CI: 0.62-1.02, n = 70 studies, p < 0.001). This trend remained in the sensitivity and subgroup analyses by world regions of studies, assay methods, and insulin resistance. No significant differences were observed in circulating vitamin B12 (SMD: -0.11; 95% CI: -0.25 to 0.03; n = 17 studies, p = 0.13) and folate levels (SMD: -0.2; 95% CI: -0.68 to 0.27; n = 17 studies, p = 0.41) between patients with and without PCOS. CONCLUSIONS: (i) Patients with PCOS exhibited significantly higher homocysteine levels than those without, and (ii) no significant differences were observed in both vitamin B12 and folate levels in women with and without PCOS. REGISTRATION: PROSPERO ID (CRD42023432883).

The use of propionic and lactic acid bacteria to produce cobalamin and folate in injera, an Ethiopian cereal-based fermented food.

Like in many developing countries, the traditional Ethiopian diet relies mainly on starchy staple foods and often lacks sufficient animal-sourced foods which are crucial for cobalamin intake. Furthermore, the concentration of folate in traditionally prepared injera, an Ethiopian cereal-based fermented staple food, is highly variable and injera contains biologically inactive corrinoids. This study aimed to improve the cobalamin and folate content of injera by using cobalamin-producing Propionibacterium freudenreichii and folate-producing Lactiplantibacillus plantarum strains, both individually and combined. Since injera is fermented using backslopping, we also assessed the ability of these strains to produce cobalamin and folate consistently across successive fermentation batches. Changes in the microbial ecosystem were monitored using real-time PCR. The theoretical contribution of the injera prepared using the selected strains to the cobalamin and folate intake of children and women of reproductive age was also calculated. Results showed that using the selected bacterial strains individually increased cobalamin (up to 19.2 µg/100 g of dry matter) and folate (up to 180.2 µg/100 g of dry matter) levels in the injera dough over several backslopping fermentation batches. Regular consumption of the injera with enhanced vitamin content produced using each strain alone would be capable of fulfilling the entire recommended nutrient intake for cobalamin and up to 29 % of the recommended intake for folate for children and women of reproductive age. However, when the strains were used together, the production of both vitamins was reduced. The presence of certain common endogenous bacterial species and genera exhibited significant variability, highlighting the complex response of the native microbiota to the different inoculation strategies employed. Future experiments should consider selecting a microbial consortium comprising non-competing microorganisms to ensure the simultaneous production of cobalamin and folate in fermented foods.

Associations of Acetic Acid Intake with Protein and Vitamin Intake Estimated via a Food Recording Application.

A conventional questionnaire-based assessment of acetic acid intake is based on the intake of seasonings such as mayonnaise, which could thereby lead to an underestimation. We here determine the relationships of acetic acid intake with nutrient intake estimated using a food recording app (Asken) based on meal recipes. A total of 141 individuals (48 men and 93 women) used the app for at least 7 days per month. The mean daily intake of acetic acid was 0.16 ± 0.19 g and the mean frequency of acetic acid intake was 2.77 ± 1.66 days per week. A multivariate regression analysis adjusted for age, sex, BMI, and energy intake revealed that the amount of acetic acid consumed was significantly and positively associated with the intake of protein (11.9 (5.1, 18.6), p < 0.001), cholesterol (80.7 (4.5, 156.9), p = 0.04), and all vitamins except vitamin K. The frequency of acetic acid intake was significantly and positively associated with protein (1.04 (0.20, 1.87), p = 0.015), vitamin B1 (0.3 (0.02,0.5), p = 0.031), niacin (0.5 (0.04,1.0), p = 0.032), and vitamin B12 (0.4 (0.1,0.7), p = 0.002) intake, suggesting that individuals who frequently consume acetic acid tend to consume more protein and some vitamins. Thus, the amount and frequency of acetic acid may reflect protein and vitamin intake.

Subacute combined degeneration from nitrous oxide abuse.

Nitrous oxide is an anesthetic medication which can also be recreationally abused in the form of whippet canisters. Its prolonged abuse can interfere with Vitamin B12 metabolism and lead to its functional deficiency. We report a case of a 30-year-old male who presented with generalized weakness and was found to have subacute combined degeneration (SCD) of the spinal cord. His laboratory workup showed low Vitamin B12 with elevated homocysteine and methylmalonic Co-A levels, and further questioning revealed prolonged nitrous oxide abuse. Nitrous oxide causes functional inactivation of methylcobalamin by rendering it unable to function as a coenzyme for methionine synthase enzyme. This leads to the decreased production of methionine and subsequent production of myelin. This case describes nitrous oxide abuse as an important etiology to be considered in patients presenting with weakness and myeloneuropathy and describes important imaging findings.

Association of MTHFR C677T, MTHFRA1298C and MTRRA66G gene polymorphisms with hyperhomocysteinemia and its modulation by the combined effect of vitamin B12 and folate in a hypertensive Chinese population.

BACKGROUND: In China, the MTHFR 677T allele, unlike in most Western populations, is a rare genetic variant linked to various disorders. The contributing nutritional and genetic factors to this genetic risk remain unclear. OBJECTIVE: This study aimed to elucidate the interactions between genetic variations in total homocysteine (tHcy) pathway genes, serum tHcy levels, and nutritional factors in a hypertensive Chinese population. METHODS: This study analyzed 1,304 hypertensive Chinese adults aged 18 years and older enrolled in the China Precision Nutrition and Health KAP Real World Study (CPNAS). Serum levels of vitamin B12 and folate were measured using the magnetic microparticle chemiluminescence method, and tHcy levels were measured using Hcy Assay kits. Identification of the MTHFR C677T, MTHFR A1298C, and MTRR A66G polymorphisms was performed via time-of-flight nucleic spectrometry. RESULTS: Our findings revealed significant sex differences in tHcy levels, with males exhibiting higher tHcy levels than females (13.95 µmol/L vs. 11.15 µmol/L, p < 0.001). Individuals deficient in both vitamin B12 and folate had an increased risk of H-Hcy (57.4%). In contrast, the prevalence of H-Hcy was lower among those deficient in either vitamin B12 (31.1%) or folate (23.2%) alone. Significant associations were identified between the MTHFR C677T and A1298C polymorphisms and elevated serum tHcy levels, particularly in individuals homozygous for the T allele. Conversely, the MTRR A66G genotype did not show a significant correlation with tHcy levels. Optimal vitamin B12 concentrations significantly modulated the genotypic effect on tHcy levels, with individuals having adequate vitamin B12 and folate exhibiting low tHcy levels, even among high-risk genotypes (TT). CONCLUSIONS: Adequate levels of folate and vitamin B12 significantly reduce serum tHcy concentrations and mitigate the genotypic impact on tHcy levels, highlighting the potential for targeted nutritional interventions to manage cardiovascular risks associated with hyperhomocysteinemia. TRIAL REGISTRATION: The Clinical Study Protocol for the Trial (CPNAS) has been officially registered at ClinicalTrials.gov under the identification number ChiCTR2100051983.

Subacute Combined Degeneration of the Spine: A Case Study of Delayed Diagnosis in the Emergency Department.

Subacute combined degeneration of the spine (SCDS) is a well-known disease that classically presents with progressive sensory and motor deficits and characteristic magnetic resonance imaging (MRI) findings, leading to its use as a key diagnostic tool. However, clinical and MRI findings in SCDS may be diverse, and thus, a high index of suspicion should be maintained for this disease, which can cause irreversible neurological damage if left untreated. In this article, we report the case of a 29-year-old female with significant recent life stressors and otherwise unremarkable medical history who presented with progressive weakness of the bilateral lower extremities who previously had unremarkable computed tomography (CT) and MRI completed at an outside hospital for the same symptoms, which had since continued to worsen. Her presentation at our emergency department (ED) prompted urgent evaluation with an MR cord compression study and neurology consultation. This workup resulted in an unremarkable preliminary MR read, and she was without anemia in laboratory studies. Given this, she was ultimately discharged with high suspicion for conversion disorder. After an addendum report from radiology with concern for subacute combined degeneration of the spine, she was called back to the ED where further workup revealed pernicious anemia leading to SCDS. This case highlights the importance of maintaining suspicion and avoiding premature closure in patients with reported neurological deficits.

Excess folic acid exposure increases uracil misincorporation into DNA in a tissue-specific manner in a mouse model of reduced methionine synthase expression.

BACKGROUND: Folate and vitamin B12 (B12) are cofactors in folate-mediated one-carbon metabolism (FOCM), a metabolic network that supports synthesis of nucleotides (including thymidylate, or dTMP) and methionine. FOCM impairments such as a deficiency or imbalance of cofactors can perturb dTMP synthesis, causing uracil misincorporation into DNA. OBJECTIVE: The purpose of this study was to determine how reduced expression of the B12-dependent enzyme methionine synthase (MTR) and excess dietary folic acid interact to affect folate distribution and markers of genome stability in mouse tissues. METHODS: Heterozygous Mtr knockout mice (Mtr+/-) model the FOCM-specific effects of B12 deficiency. Folate accumulation and vitamer distribution, genomic uracil levels, and phosphorylated histone γH2AX immunostaining were measured in male Mtr+/+ and Mtr+/- mice weaned to either a folate-sufficient control (C) diet (2 mg/kg folic acid) or a high folic acid (HFA) diet (20 mg/kg folic acid) for 7 weeks. RESULTS: Exposure to the HFA diet led to tissue-specific patterns of folate accumulation, with plasma, colon, kidney, and skeletal muscle exhibiting increased folate concentrations compared to control. Liver total folate did not differ. Though unmetabolized folic acid (UMFA) increased 10-fold in mouse plasma with HFA diet, UMFA accounted for less than 0.2% of total folate in liver and colon tissue. Exposure to HFA diet resulted in a shift in folate distribution in colon tissue with higher 5-methyl-THF and lower formyl-THF than in control mice. Mtr heterozygosity did not impact folate accumulation or distribution in any tissue. Mice on HFA diet exhibited higher uracil in genomic DNA and phosphorylated histone H2AX (γH2AX) foci in colon. Similar differences were not seen in liver. CONCLUSIONS: This study demonstrates that folic acid, even when consumed at high doses, does not meaningfully accumulate in mouse tissues, although high-dose folic acid shifts folate distribution and increases uracil accumulation in genomic DNA in colon tissue.

Ultrasensitive detection of holoTC for analysis of Vitamin B12 levels using Ag2MoO4 deposited PEDOT sensing platform.

Vitamin B12 is an essential micronutrient required for the proper functioning of the human body. Vitamin B12 deficiency is primarily causative of various neurolological disorders alongwith recurrence of oral ulcers and burning sensations which are early signs of condition such as pernicious anemia. Other complications associated with Vitamin B12 deficiency include risk of heart failure due to anemia, risk of developing autoimmune disorders and gastric cancer. Therefore, to obstruct these communal health issues, early detection of Vit B12 is highly needed. However, screening of vitamin B12 insufficiency is hindered by the low sensitivity of the conventional vitamin B12 test. Holotranscobalamin (holoTC) is an early indicator of the negative vitamin B12 balance as it is the first protein to decline in the serum. We report a novel impedimetric immunosensor based on flower-like poly (3,4-ethylenedioxythiophene) (PEDOT) nanostructural film impregnated with silver molybdate nanoparticles (Ag2MoO4 NPs) deposited on fluorine-doped tin oxide electrode. The prepared electrodes were characterized by Field emission scanning electron microscopy (FE-SEM) with energy-dispersive X-ray spectroscopy (EDS), X-ray diffraction (XRD), and electrochemical studies. The activated anti-holoTC antibody was immobilized and optimized to capture the target in a response time of 15 min. The electrochemical performance of the sensor was carried out by using the electrochemical impedance spectroscopy technique (EIS) and a good linear relationship between ΔRct and holoTC was obtained in the range from 0.1 pg mL-1 to 100 ng mL-1 with a detection limit of 0.093 pg mL-1. The proposed sensor was successfully applied in human serum samples for holoTC detection. The experimental results showed that the immunosensor is highly selective towards holoTC and presented an acceptable stability of 20 days with reproducibility RSD ≤4%. To the best of our knowledge, this is the first developed electrochemical immunosensor for holoTC detection.

The Critical Role of the Early Evaluation of Iron and Vitamin B12 Deficiency in Pregnancy.

Background and objective Anemia is a common hematological disorder during pregnancy, with iron deficiency (ID) being the most prevalent cause globally. It severely affects maternal and fetal health. This study aimed to investigate the prevalence of anemia and its association with iron and vitamin B12 deficiency during pregnancy. Materials and methods The study sample consisted of pregnant women attending the 3rd Clinic of Obstetrics and Gynecology, University General Hospital "Attikon", Athens, Greece, with a total of 145 women eventually analyzed. Blood samples were collected from pregnant women during the first, second, and third trimesters; hematological indices, including hemoglobin (HGB), hematocrit (HCT), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), red blood cell distribution width (RDW), ferritin, and vitamin B12, were recorded. Iron deficiency anemia was defined as HGB <11.0 g/dl in the first trimester and <10.5 g/dl in the second and third trimesters. Results Iron deficiency anemia is elevated in the course of pregnancy. A significant proportion of pregnant women had vitamin B12 deficiency during pregnancy, with the prevalence increasing from the first to the third trimester. The study also found that iron supplementation improved hematological indices; especially, pregnant women receiving divalent iron had significantly higher levels of HCT, HGB, and ferritin compared to those receiving trivalent iron. Conclusions Screening for iron deficiency anemia should be performed in all pregnant women, and appropriate oral iron therapy should be given as first-line treatment. Early recognition and management of low maternal iron levels are crucial and lead to improved maternal, fetal, and neonatal outcomes. Furthermore, unified international thresholds for ID are required for accurate assessments and appropriate iron supplementing. This study also recommends the screening of vitamin B12 levels as part of the systematic follow-up of pregnant women to identify potential deficiencies and provide appropriate supplementation. Further in-depth studies, particularly related to vitamin B12, are required to provide definitive conclusions and guidance.

Severe pancytopenia at the presentation of Imerslund-Gräsbeck syndrome in a 23-month-old Italian boy.

BACKGROUND: Imerslund-Gräsbeck syndrome (IGS) is a rare autosomal recessive disorder characterized by megaloblastic anemia due to selective cobalamin malabsorption and benign proteinuria. IGS is caused by a disfunction of the cubam receptor, which mediates the reabsorption of cobalamin in the ileum and the reuptake of albumin in renal proximal tubules. CASE PRESENTATION: We describe the case of a 23-month-old-italian infant presenting with severe pancytopenia and failure to thrive in whom the diagnosis of IGS was made and vitamin B12 replacement therapy was resolutive. Genetic analysis (NGS with CNV analysis including 214 genes involved in bone marrow failure and anemia), showed the presence of two pathogenetic variants in the AMN gene (c-208-2 A > G and c.1006 + 34_1007-31del). These variants have been previously described in the literature, but their combination has never been reported. CONCLUSIONS: Imerslund-Gräsbeck syndrome should be considered in the differential diagnosis of children with severe pancytopenia even in those without neurological involvement. This case emphasizes the importance of an early diagnosis and prompt treatment, to prevent irreversible neurological injury.

Cyanocobalamin-loaded dissolving microneedles diminish skin inflammation in vivo.

Inflammatory diseases of the skin have a considerable high prevalence worldwide and negatively impact the patients' quality of life. First-line standard therapies for these conditions inherently entail important side effects when used long-term, particularly complicating the management of chronic cases. Therefore, there is a need to develop novel therapeutic strategies to offer reliable alternative treatments. Abnormally high reactive oxygen species (ROS) levels are characteristic of this kind of illnesses, and therefore a reasonable therapeutic goal. Cyanocobalamin, also known as Vitamin B12, possesses notable antioxidant and ROS-scavenging properties which could make it a possible therapeutic alternative. However, its considerable molecular weight restricts passive diffusion through the skin and forces the use of an advanced transdermal delivery system. Here, we present several prototypes of Cyanocobalamin-loaded Dissolving Microarray Patches (B12@DMAPs) with adequate mechanical properties to effectively penetrate the stratum corneum barrier, allowing drug deposition into the skin structure. Ex vivo penetration and permeability studies noted an effective drug presence within the dermal skin layers; in vitro compatibility studies in representative cell skin cell lines such as L929 fibroblasts and HaCaT keratinocytes ensured their safe use. The in vivo efficacy of the selected prototype was tested in a delayed-type hypersensitivity murine model that mimics an inflammatory skin process. Several findings such as a reduction of MPO-related photon emission in a bioluminescence study, protection against histological damage, and decrease of inflammatory cytokines levels point out the effectivity of B12@DMAPs to downregulate the skin inflammatory environment. Overall, B12@DMAPs offer a cost-effective translational alternative for improving patients' skin healthcare.

B-vitamins and one-carbon metabolism during pregnancy: health impacts and challenges.

Folate, vitamin B12, vitamin B6 and riboflavin interact by functioning as cofactors within one-carbon metabolism (OCM), a network of interrelated cellular pathways essential for numerous biological processes, including the biosynthesis of DNA, amino acid interconversions and methylation reactions. The pathways of OCM are influenced by endocrine signals and genetic polymorphisms and are particularly responsive to relevant B-vitamin intakes. Physiological changes in healthy pregnancy, leading to a steady decline in B-vitamin status, add another layer of complexity to the regulation of OCM. Although significant advances have been made to improve our understanding of these pregnancy-related changes, no specific reference ranges yet exist for B-vitamin biomarkers in pregnancy to support normal fetal growth without depleting maternal stores. The lack of pregnancy-related criteria for adequacy of B-vitamin status is in turn a major limitation in identifying pregnant women most at risk of B-vitamin deficiency. Another challenge is that the evidence is very limited to provide a basis for establishing pregnancy-specific dietary recommendations for B-vitamins to support successful pregnancy outcomes. In terms of preventing adverse outcomes, periconceptional folic acid supplementation has a proven role, established more than 30 years ago, in protecting against neural tube defect-affected pregnancies and this has been the major focus of public health policy worldwide. This review evaluates the emerging evidence for the less well recognised role of B-vitamins in preventing hypertensive disorders in pregnancy and the intergenerational effects of B-vitamins on offspring neurodevelopment and cognitive performance during childhood. We also consider the underlying biological mechanisms.

Cognitive frailty in relation to vitamin B12 and 25-hydroxyvitamin D in an elderly population: a cross-sectional study from NHANES.

Background: Nutritional support has been identified as a potential intervention for cognitive frailty; however, the association between 25-hydroxyvitamin D [25-(OH)D], vitamin B12, and cognitive frailty remains ambiguous. Methods: This study utilized data from two cycles (2011-2012, 2013-2014) of the National Health and Nutrition Examination Survey (NHANES) to investigate this relationship. The researchers constructed a 41-item frailty index encompassing diverse aspects of physical functioning, psychological evaluation, and medical conditions, and evaluated each participant individually. The study utilized Spearman's rank correlation coefficient and univariate ordered logistic regression to assess the relationships between variables and cognitive frailty. Recursive feature elimination and cross-validation methods were employed to identify the most influential variables for building and optimizing multivariate ordered logistic regression models. Subgroup analyses and interaction tests were further conducted to validate the identified correlations. Results: The findings of this study confirm a negative linear correlation between 25-(OH)D levels and cognitive frailty in older adults. Specifically, a one-unit increase in 25-(OH)D levels was associated with a 12% reduction in the risk of cognitive frailty. The result was further supported by subgroup analyses and interaction tests. Conclusion: The existence of a negatively correlated linear association between 25-(OH)D levels and cognitive frailty in older adults is plausible, but further rigorously designed longitudinal studies are necessary to validate this relationship.

Vitamin B12 ameliorates gut epithelial injury via modulating the HIF-1 pathway and gut microbiota.

Inflammatory bowel diseases (IBDs) are immune chronic diseases characterized by recurrent episodes, resulting in continuous intestinal barrier damage and intestinal microbiota dysbiosis. Safe strategies aimed at stabilizing and reducing IBDs recurrence have been vigorously pursued. Here, we constructed a recurrent intestinal injury Drosophila model and found that vitamin B12 (VB12), an essential co-factor for organism physiological functions, could effectively protect the intestine and reduce dextran sulfate sodium-induced intestinal barrier disruption. VB12 also alleviated microbial dysbiosis in the Drosophila model and inhibited the growth of gram-negative bacteria. We demonstrated that VB12 could mitigate intestinal damage by activating the hypoxia-inducible factor-1 signaling pathway in injured conditions, which was achieved by regulating the intestinal oxidation. In addition, we also validated the protective effect of VB12 in a murine acute colitis model. In summary, we offer new insights and implications for the potential supportive role of VB12 in the management of recurrent IBDs flare-ups.

Natural resources, quantification, microbial bioconversion, and bioactivities of vitamin B12 for vegetarian diet.

Vitamin B12 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 B12 will lead to megaloblastic anemia and neuropathy. Traditionally, animal foods have been the main dietary source of vitamin B12. However, this review points to certain plant sources (such as algae, mushrooms, fermented vegetables, and fermented beans) as viable vitamin B12 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 B12 in food samples is low and is easily interfered by impurities, highly sensitive and specific analytical methods are used for the quantification of vitamin B12. The findings from this review could be instrumental in developing fortified plant-based foods that could prevent B12 deficiency in vegetarians and vegans, thereby broadening the scope of nutritional options available to those on plant-based diets.

Food-sourced guanidinoacetic acid and methylation cycle biomarkers in individuals aged one year and older: a population-based cross-sectional study.

PURPOSE: Several preliminary studies suggest dietary guanidinoacetic acid (GAA) might impact methyl group availability and/or methylation biomarkers, fueling ongoing debates. This study aimed to explore the relationship between dietary GAA intake and plasma indicators of the methylation cycle in individuals aged one year and older, using data from the 2001-2002 National Health and Nutrition Examination Survey (NHANES). METHODS: Dietary information was obtained from individuals who completed a 24-hour Dietary Recall, with total daily intake of GAA calculated by aggregating all relevant food items. Relevant variables related to the methylation cycle, such as red blood cell (RBC) folate and serum folate, vitamin B12, total homocysteine (tHCy), and methylmalonic acid (MMA), were identified from the NHANES 2001-2002 laboratory assessments. RESULTS: A total of 9,115 individuals (51.3% females) were included in the final analysis. Linear regression unveiled a significant association between higher GAA intake and diminished RBC folate (p < 0.001), serum folate (p < 0.001), and MMA levels (p = 0.007). It also revealed an elevation in tHCy levels with increased GAA intake (p < 0.001). These associations remained significant even after adjusting for demographic variables and dietary factors pertinent to the methylation cycle (p < 0.05). CONCLUSION: Our findings suggest that dietary exposure to GAA (resulting in conversion to creatine) could be considered a nutritional factor associated with the consumption of methyl groups in the general population.

Controlling functional homeostasis of ileal resident macrophages by vitamin B12 during steady state and Salmonella infection in mice.

Dietary micronutrients, particularly vitamin B12 (VB12), profoundly influence the physiological maintenance and function of intestinal cells. However, it is still unclear whether VB12 modulates the transcriptional and metabolic programming of ileal macrophages (iMacs), thereby contributing to intestinal homeostasis. Using multiomic approaches, we demonstrated that VB12 primarily supports the cell cycle activity and mitochondrial metabolism of iMacs, resulting in increased cell frequency compared to VB12 deficiency. VB12 also retained the ability to promote maintenance and metabolic regulation of iMacs during intestinal infection with Salmonella Typhimurium (STm). On the contrary, depletion of iMacs by inhibiting CSF1R signaling significantly increased host susceptibility to STm and prevented VB12-mediated pathogen reduction. These results thus suggest that regulation of VB12-dependent iMacs critically controls STm expansion, which may be of new relevance to advance our understanding of this vitamin and to strategically formulate sustainable therapeutic nutritional regimens that improve human gut health.

Nanoparticles of nucleotide-free analogue of vitamin B12 formed in protein nanocarriers and their neuroprotective activity in vivo.

Recently, we have described the first supermolecular nanoentities of vitamin B12 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 B12 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 B12 (viz. cyano- and aquacobalamins) and ACCby were performed. Nucleotide-free analogue of vitamin B12 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 B12, including hydrophobic ones, can be recommended for neuroprotection and targeted delivery.

Vitamin B12 Deficiency in Patients Taking Metformin: Pathogenesis and Recommendations.

Metformin is a cornerstone therapy for type 2 diabetes mellitus due to its glucose-lowering efficacy and additional benefits such as reducing cardiovascular mortality. However, accumulating evidence suggests an association between long-term metformin use and vitamin B12 deficiency, which can lead to serious clinical consequences. This review aims to synthesize current knowledge on the pathogenesis, prevalence, clinical implications, and management of metformin-induced vitamin B12 deficiency. Given the significant clinical implications, it is crucial to monitor and manage vitamin B12 levels in patients using metformin. This review emphasizes the importance of early detection and supplementation to prevent adverse outcomes. By analyzing the current evidence, the review aims to inform healthcare professionals about best practices for managing vitamin B12 deficiency in patients on metformin, offering insights to guide future clinical practices and research directions.

Vitamin B12 status and skeletal muscle function among elderly: A literature review and pilot study on the effect of oral vitamin B12 supplementation in improving muscle function.

Objectives: The objective of this study is to understand the role of vitamin B12 supplementation in improving skeletal muscle function among the elderly. Methods: A literature review in the Medline database was conducted to understand the association between vitamin B12 and muscle function in Section A. In Section B, 28 healthy elderly participants aged ≥60 years were recruited in a cross-sectional design for estimation of plasma vitamin B12 status and assessment of upper limb muscle strength Maximal voluntary contraction (MVC) and muscle quality (expressed as MVC/total muscle mass). Participants were grouped based on vitamin B12 status into vitamin B12-depleted (<148 pmol/L) and replete (≥148 pmol/L) groups. In a quasi-experimental study design, the vitamin B12-depleted group (n = 14) received daily oral vitamin B12 supplementation of 100 µg for 3 months. All the study measures were repeated post-supplementation. Results: Vitamin B12 deficiency was identified to contribute adversely to muscle strength, quality, and physical performance among older people in the extensive literature review. The pilot intervention study showed significant improvement in MVC and muscle quality (p < 0.050) post-vitamin B12 supplementation, comparable to the vitamin B12-replete group. Conclusions: Vitamin B12 may have a crucial role in the maintenance of muscle function. 3-month oral vitamin B12 supplementation among subclinical vitamin B12 deficient elderly improved muscle strength and quality and reached levels similar to the vitamin B12 replete group.