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1.
Am J Clin Nutr ; 119(5): 1122-1132, 2024 May.
Article En | MEDLINE | ID: mdl-38702109

BACKGROUND: Elevated serum methylmalonic acid (MMA), a marker of cobalamin (vitamin B12) deficiency, has been linked to cancer progression. However, the impact of MMA or cobalamin on mortality risk in cancer survivors remains unknown. OBJECTIVES: To explore the relationship between MMA, serum, dietary, and supplement of cobalamin, MMA metabolism-related genes, and poor prognosis in adult cancer survivors. METHODS: We analyzed data from 1988 cancer survivors aged ≥20 y. Patients were selected from the National Health and Nutrition Examination Survey and followed up until December 31, 2019. Weighted Cox proportional hazard regression was used to estimate hazard ratios (HRs) and the corresponding 95% confidence intervals (CIs) for mortality risk assessment. Genomic analysis identified MMA metabolism-related genes linked to early death in a 33-cancer-type cohort from The Cancer Genome Atlas. RESULTS: Among 1988 participants, 872 deaths occurred over a 10-year follow-up. Higher serum MMA levels were significantly linked to increased long-term mortality risk (tertile 3 compared with tertile 1: adjusted HR: 1.37; 95% CI: 1.11, 1.70; P-trend < 0.001). No associations were found between serum, dietary, and supplement of cobalamin and cancer survivor mortality (each P-trend > 0.143). However, MMA-associated mortality was notable in patients without deficiency. When combining cobalamin and MMA categories, multivariate-adjusted HR (95% CI) for all-cause mortality was 2.06 (95% CI: 1.60, 2.65) in participants with >250 nmol/L and cobalamin >295.1 pmol/L compared with those with MMA ≤250 nmol/L and cobalamin >295.1 pmol/L. Moreover, reduced transcriptional levels of MMA metabolism-related genes, indicating decreased mitochondrial MMA metabolism capability, are linked to an unfavorable prognosis in certain cancer types. CONCLUSIONS: Serum MMA was associated with long-term mortality risk in adult cancer survivors, which was more significant among individuals with higher levels of serum cobalamin. These findings suggest that mortality related to MMA was attributed to the insufficient flux of MMA metabolism, not cobalamin deficiency.


Biomarkers , Cancer Survivors , Methylmalonic Acid , Vitamin B 12 , Humans , Methylmalonic Acid/blood , Vitamin B 12/blood , Female , Male , Prospective Studies , Middle Aged , Biomarkers/blood , Adult , Neoplasms/mortality , Neoplasms/blood , Cohort Studies , Aged , Risk Factors
2.
Pediatr Allergy Immunol ; 35(5): e14135, 2024 May.
Article En | MEDLINE | ID: mdl-38700373

BACKGROUND: Autoimmune lymphoproliferative syndrome (ALPS) is a rare primary immune disorder caused by defect of the extrinsic apoptotic pathway. The current diagnostic criteria combine clinical features and typical biomarkers but have not been the object of clear international consensus. METHODS: We conducted a retrospective study on pediatric patients who were investigated for autoimmune cytopenia and/or lymphoproliferation at the CHU Sainte-Justine Hospital over 10 years. Patients were screened using the combination of TCRαß+ CD4- CD8- "double negative" (DN) T cells and soluble plasmatic FAS ligand (sFASL). RESULTS: Among the 398 tested patients, the median sFASL and DN T cells were 200 ng/mL and 1.8% of TCRαß+ T cells, respectively. sFASL was highly correlated with vitamin B12 levels. We identified five patients diagnosed with ALPS for whose sFASL and vitamin B12 levels were the more discriminating biomarkers. While ALPS diagnostic criteria had high sensibility, their predictive value remained low. CONCLUSION: sFASL level can efficiently discriminate patients with ALPS when using the appropriate thresholds. Our study highlights the need for an international consensus to redefine the place and threshold of biological biomarkers for ALPS diagnosis.


Autoimmune Lymphoproliferative Syndrome , Biomarkers , Fas Ligand Protein , Humans , Biomarkers/blood , Male , Female , Retrospective Studies , Child , Autoimmune Lymphoproliferative Syndrome/diagnosis , Autoimmune Lymphoproliferative Syndrome/blood , Child, Preschool , Infant , Fas Ligand Protein/blood , Adolescent , Vitamin B 12/blood
3.
Int J Mol Sci ; 25(9)2024 May 02.
Article En | MEDLINE | ID: mdl-38732193

One-carbon (1-C) metabolic deficiency impairs homeostasis, driving disease development, including infertility. It is of importance to summarize the current evidence regarding the clinical utility of 1-C metabolism-related biomolecules and methyl donors, namely, folate, betaine, choline, vitamin B12, homocysteine (Hcy), and zinc, as potential biomarkers, dietary supplements, and culture media supplements in the context of medically assisted reproduction (MAR). A narrative review of the literature was conducted in the PubMed/Medline database. Diet, ageing, and the endocrine milieu of individuals affect both 1-C metabolism and fertility status. In vitro fertilization (IVF) techniques, and culture conditions in particular, have a direct impact on 1-C metabolic activity in gametes and embryos. Critical analysis indicated that zinc supplementation in cryopreservation media may be a promising approach to reducing oxidative damage, while female serum homocysteine levels may be employed as a possible biomarker for predicting IVF outcomes. Nonetheless, the level of evidence is low, and future studies are needed to verify these data. One-carbon metabolism-related processes, including redox defense and epigenetic regulation, may be compromised in IVF-derived embryos. The study of 1-C metabolism may lead the way towards improving MAR efficiency and safety and ensuring the lifelong health of MAR infants.


Carbon , Reproductive Techniques, Assisted , Humans , Carbon/metabolism , Vitamin B 12/metabolism , Fertilization in Vitro/methods , Female , Homocysteine/metabolism , Homocysteine/blood , Folic Acid/metabolism , Dietary Supplements , Choline/metabolism , Zinc/metabolism , Betaine/metabolism , Biomarkers
4.
Isr Med Assoc J ; 26(5): 294-298, 2024 May.
Article En | MEDLINE | ID: mdl-38736344

BACKGROUND: The recreational use of nitrous oxide (N2O) has increased in recent years with a noticeable surge in the incidence of nitrous oxide-related myeloneuropathy. OBJECTIVES: To raise awareness of increasing myeloneuropathy due to recreational nitrous oxide misuse in Israel. METHODS: We conducted a case series documenting the clinical and investigative features of eight patients presenting with nitrous oxide-induced myeloneuropathy who were admitted to our departments. RESULTS: Paresthesia was the chief complaint in all patients, with sensory gait ataxia being a common feature, which was often accompanied by Romberg's sign and mild lower limb weakness. Vitamin B12 levels were below the normal range in seven patients, accompanied by elevated homocysteine and methylmalonic acid levels. Magnetic resonance imaging scans revealed hyperintense signals in the dorsal columns of the cervical spine. All patients improved following vitamin B12 injections. CONCLUSIONS: Enhancing awareness, prompting the use of appropriate investigations, and advocating for timely treatment are needed to overcome the risks associated with nitrous oxide misuse.


Magnetic Resonance Imaging , Nitrous Oxide , Vitamin B 12 , Humans , Nitrous Oxide/adverse effects , Nitrous Oxide/administration & dosage , Male , Adult , Vitamin B 12/administration & dosage , Female , Israel/epidemiology , Magnetic Resonance Imaging/methods , Spinal Cord Diseases/chemically induced , Paresthesia/chemically induced , Paresthesia/diagnosis , Middle Aged , Recreational Drug Use , Gait Ataxia/chemically induced , Gait Ataxia/etiology , Young Adult , Substance-Related Disorders/complications , Vitamin B 12 Deficiency/chemically induced , Vitamin B 12 Deficiency/diagnosis
5.
Molecules ; 29(9)2024 May 01.
Article En | MEDLINE | ID: mdl-38731585

The techniques used to detect and quantify cyanocobalamin (vitamin B12) vary considerably in terms of detection sensitivity, from the most sensitive, based on radioisotopes and mass spectrometry (MS) with limits of detection (LOD) in fg mL-1, to fluorescence (FL) and surface plasmon resonance (SPR) biosensors with LOD values in the range of a few µg mL-1. For accurate quantification of an analyte present at trace levels in complex biological matrices, a selective separation and enrichment step is required to overcome matrix interferences and ensure sufficient detection sensitivity. In this study, iron oxide magnetic nanoparticles (IONPs) were used for the extraction and initial preconcentration of cyanocobalamin (vitamin B12). In the dependence of the magnetization on the H-field (hysteresis loop), no coercivity and remanence values were found at 300 K, indicating the superparamagnetic properties of the tested IONPs. Perfluorinated acids were used as amphiphilic agents to allow the sorption of cyanocobalamin onto the IONPs. FT-IR/ATR spectroscopy was used to confirm the sorption of cyanocobalamin on the IONPs. The influence of the addition of a homologous series of perfluorinated acids such as trifluoroacetic acid (TFAA), heptafluorobutyric acid (HFBA), and trichloroacetic acid (TCAA) to the extraction mixture was tested considering their type, mass, and time required for effective sorption. The adsorption kinetics and isotherm, described by the Freundlich and Langmuir equations, were analyzed. The maximum adsorption capacity (qm) exceeded 6 mg g-1 and was 8.9 mg g-1 and 7.7 mg g-1 for HFBA and TCAA, respectively, as the most efficient additives. After the desorption process using aqueous KH2PO4 solution, the sample was finally analyzed spectrophotometrically and chromatographically. The IONP-based method was successfully applied for the isolation of cyanocobalamin from human urine samples. The results showed that the developed approach is simple, cheap, accurate, and efficient for the determination of traces of cyanocobalamin in biological matrices.


Magnetic Iron Oxide Nanoparticles , Vitamin B 12 , Vitamin B 12/chemistry , Vitamin B 12/analysis , Adsorption , Magnetic Iron Oxide Nanoparticles/chemistry , Limit of Detection , Porosity , Spectroscopy, Fourier Transform Infrared
6.
Int J Mol Sci ; 25(9)2024 May 06.
Article En | MEDLINE | ID: mdl-38732262

Vitamin B12 (cobalamin) is an essential nutrient for humans and animals. Metabolically active forms of B12-methylcobalamin and 5-deoxyadenosylcobalamin are cofactors for the enzymes methionine synthase and mitochondrial methylmalonyl-CoA mutase. Malfunction of these enzymes due to a scarcity of vitamin B12 leads to disturbance of one-carbon metabolism and impaired mitochondrial function. A significant fraction of the population (up to 20%) is deficient in vitamin B12, with a higher rate of deficiency among elderly people. B12 deficiency is associated with numerous hallmarks of aging at the cellular and organismal levels. Cellular senescence is characterized by high levels of DNA damage by metabolic abnormalities, increased mitochondrial dysfunction, and disturbance of epigenetic regulation. B12 deficiency could be responsible for or play a crucial part in these disorders. In this review, we focus on a comprehensive analysis of molecular mechanisms through which vitamin B12 influences aging. We review new data about how deficiency in vitamin B12 may accelerate cellular aging. Despite indications that vitamin B12 has an important role in health and healthy aging, knowledge of the influence of vitamin B12 on aging is still limited and requires further research.


Aging , Inflammation , Vitamin B 12 Deficiency , Vitamin B 12 , Humans , Vitamin B 12/metabolism , Animals , Aging/metabolism , Vitamin B 12 Deficiency/metabolism , Inflammation/metabolism , Epigenesis, Genetic , Cellular Senescence , Mitochondria/metabolism , DNA Damage
7.
Nutrients ; 16(7)2024 Mar 28.
Article En | MEDLINE | ID: mdl-38613029

Methionine dependence is a characteristic of most cancer cells where they are unable to proliferate when the essential amino acid methionine is replaced with its precursor homocysteine in the growing media. Normal cells, on the other hand, thrive under these conditions and are referred to as methionine-independent. The reaction that adds a methyl group from 5-methyltetrahydrofolate to homocysteine to regenerate methionine is catalyzed by the enzyme methionine synthase with the cofactor cobalamin (vitamin B12). However, decades of research have shown that methionine dependence in cancer is not due to a defect in the activity of methionine synthase. Cobalamin metabolism has been tied to the dependent phenotype in rare cell lines. We have identified a human colorectal cancer cell line in which the cells regain the ability to proliferation in methionine-free, L-homocystine-supplemented media when cyanocobalamin is supplemented at a level of 1 µg/mL. In human SW48 cells, methionine replacement with L-homocystine does not induce any measurable increase in apoptosis or reactive oxygen species production in this cell line. Rather, proliferation is halted, then restored in the presence of cyanocobalamin. Our data show that supplementation with cyanocobalamin prevents the activation of the integrated stress response (ISR) in methionine-deprived media in this cell line. The ISR-associated cell cycle arrest, characteristic of methionine-dependence in cancer, is also prevented, leading to the continuation of proliferation in methionine-deprived SW48 cells with cobalamin. Our results highlight differences between cancer cell lines in the response to cobalamin supplementation in the context of methionine dependence.


Colorectal Neoplasms , Methionine , Humans , Methionine/pharmacology , 5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase , Vitamin B 12/pharmacology , Homocystine , Racemethionine , Cell Line , Homocysteine , Colorectal Neoplasms/drug therapy
8.
Saudi Med J ; 45(4): 356-361, 2024 Apr.
Article En | MEDLINE | ID: mdl-38657991

OBJECTIVES: To assess the rate of inappropriate repetition of laboratory testing and estimate the cost of such testing for thyroid stimulating hormone (TSH), total cholesterol, vitamin D, and vitamin B12 tests. METHODS: A retrospective cohort study was carried out in the Family Medicine and Polyclinic Department at King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia. Clinical and laboratory data were collected between 2018-2021 for the 4 laboratory tests. The inappropriate repetition of tests was defined according to international guidelines and the costs were calculated using the hospital prices. RESULTS: A total of 109,929 laboratory tests carried out on 23,280 patients were included in this study. The percentage of inappropriate tests, as per the study criteria, was estimated to be 6.1% of all repeated tests. Additionally, the estimated total cost wasted amounted to 2,364,410 Saudi Riyals. Age exhibited a weak positive correlation with the total number of inappropriate tests (r=0.196, p=0.001). Furthermore, significant differences were observed in the medians of the total number of inappropriate tests among genders and nationalities (p<0.001). CONCLUSION: The study identified significantly high rates of inadequate repetitions of frequently requested laboratory tests. Urgent action is therefore crucial to overcoming such an issue.


Tertiary Healthcare , Humans , Retrospective Studies , Female , Saudi Arabia , Male , Middle Aged , Adult , Tertiary Healthcare/statistics & numerical data , Unnecessary Procedures/statistics & numerical data , Unnecessary Procedures/economics , Ambulatory Care/statistics & numerical data , Ambulatory Care/economics , Thyrotropin/blood , Aged , Young Adult , Cholesterol/blood , Vitamin B 12/blood , Vitamin D/blood , Cohort Studies , Clinical Laboratory Techniques/economics , Clinical Laboratory Techniques/statistics & numerical data , Adolescent , Value-Based Health Care
9.
Food Microbiol ; 121: 104525, 2024 Aug.
Article En | MEDLINE | ID: mdl-38637087

The lack of vitamin B12 in unprocessed plant-based foods can lead to health problems in strict vegetarians and vegans. The main aim of this study was to investigate the potential synergy of co-culturing Bifidobacterium animalis subsp. lactis and Propionibacterium freudenreichii in improving production of vitamin B12 and short-chain fatty acids in soy whey. Different strategies including mono-, sequential and simultaneous cultures were adopted. Growth, short-chain fatty acids and vitamin B12 were assessed throughout the fermentation while free amino acids, volatiles, and isoflavones were determined on the final day. P. freudenreichii monoculture grew well in soy whey, whereas B. lactis monoculture entered the death phase by day 4. Principal component analysis demonstrates that metabolic changes in both sequential cultures did not show drastic differences to those of P. freudenreichii monoculture. However, simultaneous culturing significantly improved vitamin B12, acetic acid and propionic acid contents (1.3 times, 5 times, 2.5 times, compared to the next highest treatment [sequential cultures]) in fermented soy whey relative to other culturing modes. Hence, co-culturing of P. freudenreichii and B. lactis would provide an alternative method to improve vitamin B12, acetic acid and propionic acid contents in fermented foods.


Bifidobacterium animalis , Propionibacterium freudenreichii , Propionates , Propionibacterium freudenreichii/metabolism , Bifidobacterium animalis/metabolism , Whey , Vitamin B 12/analysis , Vitamin B 12/metabolism , Propionibacterium/metabolism , Fatty Acids, Volatile/metabolism , Fermentation , Acetic Acid/metabolism , Whey Proteins/metabolism , Vitamins/metabolism
10.
PLoS One ; 19(4): e0297976, 2024.
Article En | MEDLINE | ID: mdl-38630748

BACKGROUND: Vitamin B12 deficiency is responsible for a variety of complications, particularly neurological/neuropsychiatric complications, including depression, irritability, paresthesia and insomnia. Since vitamin B12 is found in animal-derived products, vegans/vegetarians are at a greater risk for developing vitamin B12 deficiency. AIMS: This study aims to investigate the occurrence of vitamin B12 deficiency among a sample of adult Lebanese population, with a particular emphasis on assessing the severity of its neurological/neuropsychiatric signs and symptoms, especially among vegans/vegetarians. METHODOLOGY: A cross-sectional study was conducted among a sample of 483 Lebanese adults. Data was collected through a standardized questionnaire that included socio-demographic characteristics, the Patient Health Questionnaire-9 (PHQ-9), Generalized anxiety disorders-7 (GAD-7), and the Insomnia Severity Index (ISI) scales. RESULTS: Among the participants, 11.4% were in the vegan/vegetarian group, and about 43.1% had vitamin B12 deficiency. After analyzing the PHQ-9, GAD-7 and ISI total scores, higher scores were reported in participants with vitamin B12 deficiency, compared to individuals with normal vitamin B12 serum levels (p < 0.001). Regarding the diet type, vegans/vegetarians were more susceptible to developing depression compared to omnivores (mean scores of 11.92 vs 8.02 on the PHQ-9 scale, respectively, with p < 0.001). Of the patients with vitamin B12 deficiency, 81.1% reported having paresthesia compared to 43.7% of individuals with no vitamin B12 deficiency (p < 0.001). CONCLUSION: Vitamin B12 deficiency in Lebanon is notably high and is linked to an increased risk of developing depression, generalized anxiety disorder, insomnia, and paresthesia. Vegans/vegetarians exhibit a higher susceptibility to developing depression compared to omnivores, whereas the risk of developing insomnia, generalized anxiety disorder and paresthesia was statistically insignificant when comparing vegans/vegetarians to omnivores.


Sleep Initiation and Maintenance Disorders , Vitamin B 12 Deficiency , Adult , Humans , Vegans , Cross-Sectional Studies , Diet, Vegetarian , Sleep Initiation and Maintenance Disorders/complications , Paresthesia , Lebanon , Vegetarians , Diet, Vegan , Vitamin B 12 , Diet
11.
Int J Mol Sci ; 25(8)2024 Apr 10.
Article En | MEDLINE | ID: mdl-38673755

Natronorubrum daqingense JX313T is an extremely halophilic archaea that can grow in a NaCl-saturated environment. The excellent salt tolerance of N. daqingense makes it a high-potential candidate for researching the salt stress mechanisms of halophilic microorganisms from Natronorubrum. In this study, transcriptome analysis revealed that three genes related to the biosynthesis of vitamin B12 were upregulated in response to salt stress. For the wild-type (WT) strain JX313T, the low-salt adaptive mutant LND5, and the vitamin B12 synthesis-deficient strain ΔcobC, the exogenous addition of 10 mg/L of vitamin B12 could maximize their cell survival and biomass in both optimal and salt stress environments. Knockout of cobC resulted in changes in the growth boundary of the strain, as well as a significant decrease in cell survival and biomass, and the inability to synthesize vitamin B12. According to the HPLC analysis, when the external NaCl concentration (w/v) increased from 17.5% (optimal) to 22.5% (5% salt stress), the intracellular accumulation of vitamin B12 in WT increased significantly from (11.54 ± 0.44) mg/L to (15.23 ± 0.20) mg/L. In summary, N. daqingense is capable of absorbing or synthesizing vitamin B12 in response to salt stress, suggesting that vitamin B12 serves as a specific compatible solute effector for N. daqingense during salt stress.


Gene Expression Profiling , Salt Stress , Vitamin B 12 , Vitamin B 12/metabolism , Sodium Chloride/pharmacology , Transcriptome , Salt Tolerance/genetics , Gene Expression Regulation, Archaeal
12.
Zhongguo Dang Dai Er Ke Za Zhi ; 26(4): 371-377, 2024 Apr 15.
Article Zh | MEDLINE | ID: mdl-38660901

OBJECTIVES: To investigate the levels of serum folate and vitamin B12 (VB12) and their association with the level of neurodevelopment in preschool children with autism spectrum disorder (ASD). METHODS: A total of 324 ASD children aged 2-6 years and 318 healthy children aged 2-6 years were recruited. Serum levels of folate and VB12 were measured using chemiluminescent immunoassay. The Social Responsiveness Scale and the Childhood Autism Rating Scale were used to assess the core symptoms of ASD children, and the Gesell Developmental Schedule was employed to evaluate the level of neurodevelopment. RESULTS: The levels of serum folate and VB12 in ASD children were significantly lower than those in healthy children (P<0.05). Serum folate levels in ASD children were positively correlated with gross and fine motor developmental quotients (P<0.05), and serum VB12 levels were positively correlated with adaptive behavior, fine motor, and language developmental quotients (P<0.05). In ASD children aged 2 to <4 years, serum folate levels were positively correlated with developmental quotients in all domains (P<0.05), and serum VB12 levels were positively correlated with language developmental quotient (P<0.05). In male ASD children, serum VB12 levels were positively correlated with language and personal-social developmental quotients (P<0.05). CONCLUSIONS: Serum folate and VB12 levels in preschool ASD children are lower than those in healthy children and are associated with neurodevelopmental levels, especially in ASD children under 4 years of age. Therefore, maintaining normal serum folate and VB12 levels may be beneficial for the neurodevelopment of ASD children, especially in ASD children under 4 years of age.


Autism Spectrum Disorder , Folic Acid , Vitamin B 12 , Humans , Autism Spectrum Disorder/blood , Autism Spectrum Disorder/etiology , Child, Preschool , Male , Female , Folic Acid/blood , Vitamin B 12/blood , Child , Child Development
13.
J Nutr Sci Vitaminol (Tokyo) ; 70(2): 139-149, 2024.
Article En | MEDLINE | ID: mdl-38684384

Since propionate exerts several physiological effects, maintenance of its normal colonic fermentation is essential. To investigate whether vitamin B12 (VB12) is essential for normal propionate fermentation by colonic bacteria, via the succinate pathway, we examined if high-amylose cornstarch (HACS) feeding activated such a pathway, if high HACS feeding impaired propionate fermentation, and if oral VB12 supplementation normalized propionate fermentation. Male rats were given control, 20% HACS or 3% fucose diets (Expt. 1); a VB12-free control diet or one supplemented with 5-30% HACS (Expt. 2); and the 20% HACS diet supplemented with 0.025-25 mg/kg of VB12 (Expt. 3), for 14 d. HACS feeding significantly increased cecal succinate concentration, activating the succinate pathway (Expt. 1). Cecal cobalamin concentration in 20% and 30% HACS groups was about 75% of that in the control group (Expt. 2). Cecal succinate and propionate concentrations significantly increased and decreased in 30% HACS groups, respectively, compared with the control group. Although HACS group supplemented with 0.025 mg/kg of VB12 had a low concentration of cecal propionate, adding high amounts of VB12 to HACS diets provided sufficient amounts of VB12 to rat ceca and increased cecal propionate concentration (Expt. 3). Compared with the non-HACS group, the relative abundance of Akkermansia muciniphila, but not Bacteroides/Phocaeicola, was lower in the HACS counterpart and showed improvement with increased VB12 doses. To summarize, feeding high HACS decreased and increased cecal VB12 and succinate concentrations, respectively. Furthermore, colonic delivery of sufficient amounts of VB12 to rats likely reduced accumulation of succinate and normalized propionate fermentation.


Amylose , Cecum , Colon , Dietary Supplements , Fermentation , Propionates , Starch , Vitamin B 12 , Animals , Male , Propionates/metabolism , Cecum/microbiology , Cecum/metabolism , Vitamin B 12/administration & dosage , Vitamin B 12/pharmacology , Colon/metabolism , Colon/microbiology , Starch/metabolism , Starch/administration & dosage , Amylose/administration & dosage , Amylose/metabolism , Rats , Succinic Acid/metabolism , Diet , Rats, Wistar , Rats, Sprague-Dawley
14.
Molecules ; 29(8)2024 Apr 15.
Article En | MEDLINE | ID: mdl-38675615

This study presents a new technique for determining vitamin B12 in milk powder using high-performance liquid chromatography-inductively coupled plasma mass spectrometry (HPLC-ICP-MS). We used ultrasonics with potassium ferrocyanide and zinc acetate solutions to extract the samples. 59Co was employed as the analytical target for cyanocobalamin. It was separated using a Phenomenex Luna 5 µm C18 (250 × 4.6 mm) chromatographic column with a mobile phase consisting of 1.6 mmol/L EDTA and 0.4 mmol/L KH2PO4 in a 60% v/v methanol solution (pH = 4.0). The sample has an excellent separating degree for free cobalt and cyanocobalamin, and isocratic elution can be finished within 4.0 min. To eliminate the matrix interference due to the presence of milk powder, we applied collision mode (KED). The linear range of cyanocobalamine ranged from 1.0 µg/L to 20 µg/L, with correlation coefficients (r2) of 0.9994. The limit of detection (LOD) was 0.63 µg/kg, and the limit of quantitation (LOQ) was 2.11 µg/kg. The mean recoveries were in the range of 87.4-103.6%. The accuracy and precision of the developed method are well suited for the fast quantification of the trace vitamin B12 in milk powder.


Mass Spectrometry , Milk , Vitamin B 12 , Vitamin B 12/analysis , Chromatography, High Pressure Liquid/methods , Milk/chemistry , Animals , Mass Spectrometry/methods , Limit of Detection , Powders/chemistry , Reproducibility of Results
15.
Biochemistry (Mosc) ; 89(3): 562-573, 2024 Mar.
Article En | MEDLINE | ID: mdl-38648773

The contents of homocysteine (HCy), cyanocobalamin (vitamin B12), folic acid (vitamin B9), and pyridoxine (vitamin B6) were analyzed and the genotypes of the main gene polymorphisms associated with folate metabolism (C677T and A1298C of the MTHFR gene, A2756G of the MTR gene and A66G of the MTRR gene) were determined in children at the onset of multiple sclerosis (MS) (with disease duration of no more than six months), healthy children under 18 years (control group), healthy adults without neurological pathology, adult patients with MS at the onset of disease, and adult patients with long-term MS. A significant increase in the HCy levels was found in children at the MS onset compared to healthy children of the corresponding age. It was established that the content of HCy in children has a high predictive value. At the same time, an increase in the HCy levels was not accompanied by the deficiency of vitamins B6, B9, and B12 in the blood. The lack of correlation between the laboratory signs of vitamin deficiency and HCy levels may be due to the polymorphic variants of folate cycle genes. An increased HCy level should be considered as a marker of functional disorders of folate metabolism accompanying the development of pathological process in pediatric MS. Our finding can be used to develop new approaches to the prevention of demyelination in children and treatment of pediatric MS.


5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase , Folic Acid , Homocysteine , Methylenetetrahydrofolate Reductase (NADPH2) , Multiple Sclerosis , Humans , Homocysteine/blood , Homocysteine/metabolism , Multiple Sclerosis/blood , Multiple Sclerosis/genetics , Multiple Sclerosis/metabolism , Folic Acid/blood , Folic Acid/metabolism , Female , Male , Child , Methylenetetrahydrofolate Reductase (NADPH2)/genetics , Methylenetetrahydrofolate Reductase (NADPH2)/deficiency , Methylenetetrahydrofolate Reductase (NADPH2)/metabolism , 5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase/genetics , 5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase/metabolism , Adult , Adolescent , Vitamin B Deficiency/complications , Vitamin B Deficiency/metabolism , Vitamin B Deficiency/blood , Ferredoxin-NADP Reductase/genetics , Ferredoxin-NADP Reductase/metabolism , Vitamin B 12/blood , Vitamin B 12/metabolism , Age of Onset
16.
PLoS One ; 19(4): e0302500, 2024.
Article En | MEDLINE | ID: mdl-38662670

Metformin is a cornerstone medication in the management of type 2 diabetes. Metformin is safe, effective, and inexpensive; however, it is associated with vitamin B12 deficiency. This study set out to evaluate the rate of vitamin B12 deficiency in Vietnamese patients with type 2 diabetes who were treated with metformin and to investigate factors associated with vitamin B12 deficiency. This is a cross-sectional study that was conducted in Vinmec Central Park Hospital from February to June 2023. The clinical and paraclinical characteristics of the participants were recorded, and the levels of vitamin B12 and folate were measured. The rate of vitamin B12 deficiency in patients treated with metformin was found to be 18.6%. Further, the duration of diabetes, duration of metformin use, metformin dose, and hemoglobin levels were statistically associated with vitamin B12 deficiency with OR (95% CI) = 1.12 (1.03-1.19), 1.01 (1.00-1.02), 1.002 (1.001-1.002), 0.74 (0.55-0.99), respectively. After adjusting for covariates, a metformin dose greater than the median dose remained the only parameter associated with vitamin B12 deficiency, with OR (95% CI) = 4.10 (1.62-10.36). Moreover, when combining both long-term use of metformin and a metformin dose greater than the median dose, the OR increased to 5.25 (95% CI: 2.11-13.15). These results demonstrate that vitamin B12 deficiency in patients treated with metformin is quite prevalent in Vietnam and that those with long-term use of metformin (48 months or more) and high metformin dose (1000 mg/day or more) are at high risk of experiencing this adverse effect and so require screening.


Diabetes Mellitus, Type 2 , Hypoglycemic Agents , Metformin , Vitamin B 12 Deficiency , Humans , Metformin/therapeutic use , Metformin/adverse effects , Vitamin B 12 Deficiency/chemically induced , Vitamin B 12 Deficiency/drug therapy , Vitamin B 12 Deficiency/epidemiology , Male , Diabetes Mellitus, Type 2/drug therapy , Female , Cross-Sectional Studies , Middle Aged , Hypoglycemic Agents/therapeutic use , Hypoglycemic Agents/adverse effects , Aged , Vitamin B 12/blood , Vietnam/epidemiology , Adult , Folic Acid/administration & dosage
17.
Biomed Environ Sci ; 37(3): 242-253, 2024 Mar 20.
Article En | MEDLINE | ID: mdl-38582989

Objective: This study aimed to evaluate the associations of serum folate and/or vitamin B 12 concentrations with obesity among Chinese children and adolescents. Methods: A cross-sectional study was conducted including 3,079 Chinese children and adolescents, aged 6 to 17 years, from Jiangsu, China. Anthropometric indices, such as, children's body mass index (BMI), BMI z-scores, waist circumference, and waist-to-height ratio were utilized. Multivariable linear regression and generalized additive models were used to investigate the associations of serum folate and vitamin B 12 levels with anthropometric indices and odds of obesity. Results: We observed that serum vitamin B 12 concentrations were inversely associated with all anthropometric indices and the odds of general obesity [odds ratio ( OR) = 0.68; 95% confidence interval ( CI) = 0.59, 0.78] and abdominal obesity ( OR = 0.68; 95% CI = 0.60, 0.77). When compared to participants with both serum vitamin levels in the two middle quartiles, those with both serum folate and vitamin B 12 levels in the highest quartile were less prone to general ( OR = 0.31, 95% CI = 0.19, 0.50) or abdominal obesity ( OR = 0.46, 95% CI = 0.31, 0.67). Conversely, participants with vitamin B 12 levels in the lowest quartile alongside folate levels in the highest quartile had higher odds of abdominal obesity ( OR = 2.06, 95% CI = 1.09, 3.91). Conclusion: Higher serum vitamin B 12 concentrations, but not serum folate concentrations, were associated with lower odds of childhood obesity. Children and adolescents with high levels of vitamin B 12 and folate were less likely to be obese.


Pediatric Obesity , Vitamin B 12 , Humans , Child , Adolescent , Obesity, Abdominal , Cross-Sectional Studies , Pediatric Obesity/epidemiology , Risk Factors , Body Mass Index , Folic Acid , Vitamins
18.
Cell Mol Biol (Noisy-le-grand) ; 70(3): 7-12, 2024 Mar 31.
Article En | MEDLINE | ID: mdl-38650163

Recurrent Aphthous stomatitis (RAS) is common oral mucosal condition. The pathophysiology of RAS is affected by a variety of variables, including microbial, genetic, immunological and local and systemic diseases. Interleukin IL-1ß, a cytokine that promotes inflammation, has been found in high concentrations in the circulation of RAS. The goal of current investigation was to determine whether RAS is connected with polymorphisms of the IL-1ß 542 T>A gene. A total of 60 RAS patients and 30 controls were included in the study. Biochemical investigations for determining (vitamin D, vitamin B12 and zinc) were done and genotypes of IL-1B gene polymorphisms were determined using polymerase chain reaction (PCR) and sequencing. The mean age of the participants was 30.83 ± 1.466 years (range 16 to 50). There was no significant association of SNP IL-1ß 542T>A polymorphism with RAS diseases compared to controls, in both parameters such as sex (p-value=0.495) and age groups (p-value=0.6253). There was significant difference in the occurrence of both A and T alleles between RAS patients and controls (p-value=0.0058). The mean vitamin D in both genotypes TA and TT differed significantly (p-value=0.007) but in genotype AA there was no significant difference. Significant difference was observed in zinc concentration between patients and controls (p-value=0.0031). The findings of current investigation indicate that there is a specific IL-1ß 542 T>A gene variation that is associated to the pathogenesis of RAS. Allele A was related to the risk of RAS in Erbil city population.


Genetic Predisposition to Disease , Interleukin-1beta , Polymorphism, Single Nucleotide , Stomatitis, Aphthous , Humans , Stomatitis, Aphthous/genetics , Interleukin-1beta/genetics , Male , Female , Adult , Polymorphism, Single Nucleotide/genetics , Middle Aged , Adolescent , Young Adult , Gene Frequency/genetics , Case-Control Studies , Alleles , Genotype , Vitamin D/blood , Vitamin B 12/blood , Zinc
19.
BMJ Case Rep ; 17(4)2024 Apr 24.
Article En | MEDLINE | ID: mdl-38663893

Vitamin B12 is required for the formation of haematopoietic cells and the synthesis of myelin. Deficiency typically presents with fatigue and megaloblastic anaemia. Prolonged deficiency can cause neurological symptoms such as paresthesia, which can progress to subacute combined degeneration of the spinal cord. We describe an unusual presentation of B12 deficiency in a young man who was initially diagnosed and treated for cervical radiculopathy. This case highlights the challenges of diagnosing B12 deficiency in patients with neurologic but without haematologic, abnormalities. While the current incidence of B12 deficiency in developed countries is low, cases are likely to rise with the increased adoption of veganism. Clinicians should be aware of the variable presentations of B12 deficiency because delayed diagnosis and treatment increases morbidity and can cause irreversible neurological deficits.


Neck Pain , Radiculopathy , Vitamin B 12 Deficiency , Vitamin B 12 , Adult , Humans , Male , Cervical Vertebrae , Diagnosis, Differential , Neck Pain/etiology , Radiculopathy/etiology , Radiculopathy/diagnosis , Vitamin B 12/therapeutic use , Vitamin B 12 Deficiency/complications , Vitamin B 12 Deficiency/diagnosis
20.
Nat Commun ; 15(1): 2626, 2024 Mar 23.
Article En | MEDLINE | ID: mdl-38521790

BacA is a mycobacterial ATP-binding cassette (ABC) transporter involved in the translocation of water-soluble compounds across the lipid bilayer. Whole-cell-based assays have shown that BacA imports cobalamin as well as unrelated hydrophilic compounds such as the antibiotic bleomycin and the antimicrobial peptide Bac7 into the cytoplasm. Surprisingly, there are indications that BacA also mediates the export of different antibacterial compounds, which is difficult to reconcile with the notion that ABC transporters generally operate in a strictly unidirectional manner. Here we resolve this conundrum by developing a fluorescence-based transport assay to monitor the transport of cobalamin across liposomal membranes. We find that BacA transports cobalamin in both the import and export direction. This highly unusual bidirectionality suggests that BacA is mechanistically distinct from other ABC transporters and facilitates ATP-driven diffusion, a function that may be important for the evolvability of specific transporters, and may bring competitive advantages to microbial communities.


ATP-Binding Cassette Transporters , Vitamin B 12 , ATP-Binding Cassette Transporters/metabolism , Membrane Transport Proteins/metabolism , Lipid Bilayers , Adenosine Triphosphate , Biological Transport
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