RESUMO
BACKGROUND: Vitamin B12 deficiency is a recognised cause of neurological manifestations, including peripheral neuropathy, behavioural changes, and seizures. However, developmental and epileptic encephalopathy due to vitamin B12 deficiency is very rare. Here, we report an infant with vitamin B12-responsive developmental and epileptic encephalopathy due to a novel mutation in the fucosyltransferase 2 (FUT2) gene responsible for vitamin B12 absorption. CASE PRESENTATION: An 11-month-old girl of non-consanguineous parents presented with recurrent episodes of seizures since four months. Her seizures started as flexor epileptic spasms occurring in clusters resembling infantile epileptic spasms syndrome with hypsarrhythmia in the electroencephalogram. She was treated with multiple drugs, including high-dose prednisolone, vigabatrin, sodium valproate, levetiracetam and clobazam, without any response, and she continued to have seizures at 11 months. She had an early developmental delay with maximally achieving partial head control and responsive smile at four months. Her development regressed with the onset of seizure; at 11 months, her developmental age was below six weeks. On examination, she was pale and had generalised hypotonia with normal muscle power and reflexes. Her full blood count and blood picture revealed macrocytic anaemia with oval and round macrocytes. Bone marrow aspiration showed hypercellular marrow erythropoiesis with normoblastic and megaloblastic maturation. Due to the unusual association of refractory epilepsy and megaloblastic anaemia, a rare genetic disease of the vitamin B12 or folate pathways was suspected. The whole exome sequencing revealed a homozygous missense variant in exon 2 of the FUT2 gene associated with reduced vitamin B12 absorption and low plasma vitamin B12 levels, confirming the diagnosis of vitamin B12 deficiency related developmental and epileptic encephalopathy. She was started on intramuscular hydroxocobalamin, for which she showed a marked response with reduced seizure frequency. CONCLUSION: We report a novel variant in the FUT2 gene associated with vitamin B12-responsive developmental and epileptic encephalopathy and megaloblastic anaemia. This case report highlights the importance of timely genetic testing in children with refractory developmental and epileptic encephalopathy to identify treatable causes.
Assuntos
Fucosiltransferases , Galactosídeo 2-alfa-L-Fucosiltransferase , Deficiência de Vitamina B 12 , Vitamina B 12 , Humanos , Feminino , Fucosiltransferases/genética , Lactente , Deficiência de Vitamina B 12/genética , Deficiência de Vitamina B 12/tratamento farmacológico , Vitamina B 12/uso terapêutico , Mutação , Espasmos Infantis/genética , Espasmos Infantis/tratamento farmacológico , Deficiências do Desenvolvimento/genéticaRESUMO
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.
Assuntos
Sulfato de Dextrana , Modelos Animais de Doenças , Microbioma Gastrointestinal , Fator 1 Induzível por Hipóxia , Mucosa Intestinal , Transdução de Sinais , Vitamina B 12 , Animais , Microbioma Gastrointestinal/efeitos dos fármacos , Vitamina B 12/farmacologia , Vitamina B 12/metabolismo , Camundongos , Mucosa Intestinal/metabolismo , Mucosa Intestinal/microbiologia , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/patologia , Transdução de Sinais/efeitos dos fármacos , Sulfato de Dextrana/toxicidade , Fator 1 Induzível por Hipóxia/metabolismo , Colite/metabolismo , Colite/induzido quimicamente , Colite/microbiologia , Colite/patologia , Colite/tratamento farmacológico , Disbiose/microbiologia , Disbiose/metabolismo , Camundongos Endogâmicos C57BL , Doenças Inflamatórias Intestinais/metabolismo , Doenças Inflamatórias Intestinais/microbiologia , Doenças Inflamatórias Intestinais/patologia , Doenças Inflamatórias Intestinais/tratamento farmacológico , Drosophila/metabolismoRESUMO
This study aimed to determine if maternal fatty acids (FA) levels during pregnancy are associated with the occurrence of neural tube defects (NTDs) and to explore the correlation between FA and maternal vitamin D, homocysteine, vitamin B12, and folate in cases. Plasma FA composition was assessed using capillary gas chromatography. Comparisons between cases and controls were performed by independent samples t-test for continuous variables. Cases had significantly higher levels of heptadecanoic acid, linolelaidic acid, and arachidonic acid (ARA):(eicosapentaenoic acid+docosahexaenoic acid) ratio than controls (p < 0.05). Nervonic acid, ARA, adrenic acid, eicosapentaenoic acid, docosahexaenoic acid, and omega-3 polyunsaturated fatty acids (n-3 PUFA) levels were significantly lower in cases (p < 0.05). Maternal 25-hydroxyvitamin D (25(OH)D) levels were positively correlated with maternal polyunsaturated fatty acids and omega-6 polyunsaturated fatty acids. RBC folate levels were negatively correlated with n-3 PUFA.Further research is required to clarify the association of FA metabolism with NTDs.
Assuntos
Ácidos Graxos , Ácido Fólico , Defeitos do Tubo Neural , Vitamina D , Humanos , Feminino , Gravidez , Defeitos do Tubo Neural/sangue , Defeitos do Tubo Neural/diagnóstico , Adulto , Ácidos Graxos/sangue , Ácidos Graxos/metabolismo , Vitamina D/sangue , Vitamina D/análogos & derivados , Ácido Fólico/sangue , Estudos de Casos e Controles , Ácidos Docosa-Hexaenoicos/sangue , Vitamina B 12/sangue , Homocisteína/sangue , Ácido Araquidônico/sangue , Ácido Araquidônico/metabolismo , Ácido Eicosapentaenoico/sangue , Ácidos Graxos Ômega-3/sangue , Ácidos Graxos Ômega-3/metabolismo , Ácidos Graxos Monoinsaturados , Ácidos Graxos InsaturadosRESUMO
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.
Assuntos
Anemia Megaloblástica , Síndromes de Malabsorção , Pancitopenia , Deficiência de Vitamina B 12 , Humanos , Pancitopenia/diagnóstico , Pancitopenia/genética , Pancitopenia/etiologia , Anemia Megaloblástica/diagnóstico , Anemia Megaloblástica/genética , Masculino , Síndromes de Malabsorção/diagnóstico , Síndromes de Malabsorção/genética , Síndromes de Malabsorção/complicações , Deficiência de Vitamina B 12/genética , Deficiência de Vitamina B 12/diagnóstico , Deficiência de Vitamina B 12/complicações , Lactente , Itália , Vitamina B 12/uso terapêutico , Cistinose/diagnóstico , Cistinose/genética , Cistinose/complicações , Proteinúria/diagnóstico , Proteinúria/etiologia , Diagnóstico Diferencial , Proteínas de MembranaRESUMO
Vitamin B12 is an essential nutritional co-factor for the folate and methionine cycles, which together constitute one-carbon metabolism. Here, we show that dietary uptake of vitamin B12 modulates cell fate decisions controlled by the conserved RAS/MAPK signaling pathway in C. elegans. A bacterial diet rich in vitamin B12 increases vulval induction, germ cell apoptosis and oocyte differentiation. These effects are mediated by different one-carbon metabolites in a tissue-specific manner. Vitamin B12 enhances via the choline/phosphatidylcholine metabolism vulval induction by down-regulating fat biosynthesis genes and increasing H3K4 tri-methylation, which results in increased expression of RAS/MAPK target genes. Furthermore, the nucleoside metabolism and H3K4 tri-methylation positively regulate germ cell apoptosis and oocyte production. Using mammalian cells carrying different activated KRAS and BRAF alleles, we show that the effects of methionine on RAS/MAPK-regulated phenotype are conserved in mammals. Our findings suggest that the vitamin B12-dependent one-carbon metabolism is a limiting factor for diverse RAS/MAPK-induced cellular responses.
Assuntos
Apoptose , Caenorhabditis elegans , Diferenciação Celular , Metionina , Vitamina B 12 , Animais , Vitamina B 12/metabolismo , Vitamina B 12/farmacologia , Caenorhabditis elegans/metabolismo , Caenorhabditis elegans/genética , Feminino , Metionina/metabolismo , Apoptose/efeitos dos fármacos , Oócitos/metabolismo , Proteínas de Caenorhabditis elegans/metabolismo , Proteínas de Caenorhabditis elegans/genética , Proteínas ras/metabolismo , Carbono/metabolismo , Vulva/metabolismo , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Células Germinativas/metabolismo , Colina/metabolismo , Fosfatidilcolinas/metabolismo , Camundongos , Humanos , Histonas/metabolismo , Transdução de SinaisRESUMO
BACKGROUND: Microbial pdu and cob-cbi-hem gene clusters encode the key enzyme glycerol/diol dehydratase (PduCDE), which mediates the transformation of dietary nutrients glycerol and 1,2-propanediol (1,2-PD) to a variety of metabolites, and enzymes for cobalamin synthesis, a co-factor and shared good of microbial communities. It was the aim of this study to relate pdu as a multipurpose functional trait to environmental conditions and microbial community composition. We collected fecal samples from wild animal species living in captivity with different gut physiology and diet (n = 55, in total 104 samples), determined occurrence and diversity of pdu and cob-cbi-hem using a novel approach combining metagenomics with quantification of metabolic and genetic biomarkers, and conducted in vitro fermentations to test for trait-based activity. RESULTS: Fecal levels of the glycerol transformation product 1,3-propanediol (1,3-PD) were higher in hindgut than foregut fermenters. Gene-based analyses indicated that pduC harboring taxa are common feature of captive wild animal fecal microbiota that occur more frequently and at higher abundance in hindgut fermenters. Phylogenetic analysis of genomes reconstructed from metagenomic sequences identified captive wild animal fecal microbiota as taxonomically rich with a total of 4150 species and > 1800 novel species but pointed at only 56 species that at least partially harbored pdu and cbi-cob-hem. While taxonomic diversity was highest in fecal samples of foregut-fermenting herbivores, higher pduC abundance and higher diversity of pdu/cbi-cob-hem related to higher potential for glycerol and 1,2-PD utilization of the less diverse microbiota of hindgut-fermenting carnivores in vitro. CONCLUSION: Our approach combining metabolite and gene biomarker analysis with metagenomics and phenotypic characterization identified Pdu as a common function of fecal microbiota of captive wild animals shared by few taxa and stratified the potential of fecal microbiota for glycerol/1,2-PD utilization and cobalamin synthesis depending on diet and physiology of the host. This trait-based study suggests that the ability to utilize glycerol/1,2-PD is a key function of hindgut-fermenting carnivores, which does not relate to overall community diversity but links to the potential for cobalamin formation. Video Abstract.
Assuntos
Fezes , Fermentação , Microbioma Gastrointestinal , Glicerol , Metagenômica , Animais , Fezes/microbiologia , Glicerol/metabolismo , Metagenômica/métodos , Hidroliases/genética , Hidroliases/metabolismo , Propilenoglicóis/metabolismo , Vitamina B 12/metabolismo , Bactérias/classificação , Bactérias/genética , Bactérias/isolamento & purificação , Bactérias/enzimologia , Filogenia , Animais Selvagens/microbiologiaRESUMO
BACKGROUND: Imerslund-Gräsbeck syndrome (IGS) is an autosomal recessive disorder characterized by selective vitamin B12 malabsorption, resulting in vitamin B12 deficiency and impaired reabsorption of proximal tubular proteins.This case highlights a previously unidentified compound heterozygous variant in the Amnionless (AMN) gene that causes IGS syndrome and underscores the importance of long-term oral vitamin B12 replacement therapy in managing the condition. CASE PRESENTATION: In this retrospective analysis, we present the clinical data of a 3-year and 6-month-old female child diagnosed with IGS at Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, China, in November 2018. The child was admitted to the hospital due to a history of anemia persisting for over a month. There was no previous significant medical history. The admission examination revealed megaloblastic anemia with proteinuria. Serum vitamin B12 levels were decreased, while folic acid and renal function were normal. The patient was diagnosed with megaloblastic anemia and started long-term oral vitamin B12 replacement therapy. Throughout the follow-up period, blood tests consistently showed normal results, while proteinuria persisted. In November 2019, the child and her parents underwent whole exome sequencing analysis, which revealed a novel compound heterozygous variant in the AMN gene: c.162 + 1G > A and c.922 C > T (p.Q308X) in the child, c.162 + 1G > A in the father, and c.922 C > T (p.Q308X) in the mother. Therefore, this child was further diagnosed with IGS. CONCLUSIONS: In this case, whole exome sequencing proves to be highly practical in daily healthcare for diagnosing and refining rare or ultra-rare diseases with ambiguous phenotypes or genetic diversity. It is also valuable for prognostic evaluation and personalized management. Additionally, the oral vitamin B12 treatment demonstrated positive clinical effects for the child, offering a new option for patients unable to undergo intramuscular vitamin B12 replacement therapy.
Assuntos
Anemia Megaloblástica , Síndromes de Malabsorção , Mutação , Deficiência de Vitamina B 12 , Vitamina B 12 , Humanos , Feminino , Deficiência de Vitamina B 12/genética , Deficiência de Vitamina B 12/tratamento farmacológico , Deficiência de Vitamina B 12/diagnóstico , Anemia Megaloblástica/genética , Anemia Megaloblástica/tratamento farmacológico , Anemia Megaloblástica/diagnóstico , Síndromes de Malabsorção/genética , Síndromes de Malabsorção/diagnóstico , Pré-Escolar , Vitamina B 12/uso terapêutico , Proteínas de Membrana/genética , Heterozigoto , Estudos Retrospectivos , ProteinúriaRESUMO
Vitamin B12, 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 B12 and are typically considered not to utilize it. Some algae facultatively utilize B12 because they encode both METE and METH, while other algae are dependent on B12 as they encode METH only. We performed phylogenomic analyses of METE, METH and 11 further proteins involved in B12 metabolism across more than 1600 plant and algal genomes and transcriptomes (e.g. from OneKp), demonstrating the presence of B12-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 B12-metabolism in the last common land plant ancestor. Our data further show more limited distributions for other B12-related proteins (MCM and RNR-II) and B12 dependency in several algal orders. Finally, considering the collection sites of algae that have lost B12 metabolism, we propose freshwater-to-land transitions and symbiotic associations to have been constraining factors for B12 availability in early plant evolution. This article is part of the theme issue 'The evolution of plant metabolism'.
Assuntos
Embriófitas , Vitamina B 12 , Vitamina B 12/metabolismo , Embriófitas/genética , Embriófitas/metabolismo , Filogenia , 5-Metiltetra-Hidrofolato-Homocisteína S-Metiltransferase/metabolismo , 5-Metiltetra-Hidrofolato-Homocisteína S-Metiltransferase/genética , Evolução Molecular , Proteínas de Plantas/metabolismo , Proteínas de Plantas/genética , Evolução BiológicaRESUMO
OBJECTIVES: This study aimed to establish reference intervals (RIs) for Russian adults for hematological parameters including related iron markers and vitamins. Sources of variation of reference values (RVs) and needs for secondary exclusion were explored for proper derivations of RIs. METHODS: Following the harmonized protocol of the IFCC Committee on Reference Intervals and Decision Limits (C-RIDL), 506 healthy Russians (age 18-80; 46% male) were recruited. Complete blood counts (CBC) and leukocyte differentials, iron markers, vitamin B12, and folate were measured by Beckman Coulter's analyzers. Sources of variation were analyzed by multiple regression analysis, and ANOVAs, and the need for partitioning RVs was decided accordingly. Two schemes of excluding latent anemia were compared: (1) latent abnormal values exclusion method (LAVE) based on associations among CBC parameters, or (2) explicit exclusion of individuals with either ferritin or iron below the respective lower limit of the manufacturer. RIs were determined by the parametric method using two-parameter Box-Cox formula. RESULTS: Gender-specific RIs were required for most analytes, while age-specific RIs were set only for ferritin in females. A BMI-related increase in RVs was prominently observed for reticulocyte parameters, hence we chose to exclude individuals with BMI>28 kg/m2 when establishing the RIs. The LAVE method was more effective in excluding individuals with latent anemia, than exclusion based on low ferritin and/or iron values. International comparison revealed that Russian RIs featured a lower side shift of platelet counts. Similar to African countries, Russian RIs for total leukocyte and neutrophil counts were lower compared to most of other countries. CONCLUSION: RIs for the Russian population for 34 hematological and related parameters were established using up-to-date methods proposed by C-RIDL. Reducing the influences of latent anemia and obesity on RIs was crucial for erythrocyte parameters. Low levels of Russian RIs observed for platelet and neutrophil counts need further investigation.
Assuntos
Biomarcadores , Ferro , Vitamina B 12 , Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Federação Russa , Ferro/sangue , Idoso , Valores de Referência , Contagem de Células Sanguíneas/normas , Adulto Jovem , Adolescente , Vitamina B 12/sangue , Biomarcadores/sangue , Idoso de 80 Anos ou mais , Ácido Fólico/sangue , Ferritinas/sangue , Vitaminas/sangueRESUMO
Cobalamin (VB12) is in enormous demand across the fields of medicine, food, and feed additives. However, the oxygen supply plays a critical role in VB12 biosynthesis by Ensifer adhaerens Casida A and has been identified as a bottleneck for economical substrate consumption. This study elucidates the relationship between oxygen limitation and VB12 accumulation with transcriptomic and metabolomic analyses. Under oxygen limitation, E. adhaerens enhances oxygen transport and storage by increasing expression of flavin hemoglobin (Hmp), which was up-regulated 6-fold at 24 h of oxygen restriction compared to the oxygen restriction of 4 h (p < 0.01). Because of the cofactor of Hmp is heme, the demand for heme increases, leading to the upregulation of genes in the heme biosynthesis pathway. Similarly, genes involved in biosynthesis of its precursor, 5-ALA, were upregulated as well. 5-ALA is also a direct precursor of VB12, further leading to the upregulation of genes in the VB12 biosynthesis pathway. This process initiates biosynthesis and accumulation of VB12. As VB12 and heme biosynthesis progresses, genes associated with the biosynthesis and transportation pathways of compounds related to their biosynthesis were likewise upregulated, including genes involved in S-adenosyl methionine (SAM) biosynthesis, and the transport of Fe2+ and Co2+. Additionally, amino acids and organic acids associated with biosynthesis were also extensively consumed, such as methionine, which is used for synthesizing SAM, decreased by 310% after 24 h of oxygen limitation compared to 20% dissolved oxygen (p < 0.05). At the same time, genes related to growth-associated metabolic pathways, such as pentose phosphate pathway (PPP), were significantly downregulated. Therefore, the potential mechanism by which E. adhaerens accumulates VB12 under oxygen-limited conditions by enhancing Hmp expression, which facilitates the porphyrin metabolic pathway and promotes VB12 biosynthesis. This research provides valuable insights for increasing VB12 production through metabolic engineering and process optimization.
Assuntos
Oxigênio , Vitamina B 12 , Oxigênio/metabolismo , Vitamina B 12/metabolismo , Heme/metabolismo , Transcriptoma/genéticaRESUMO
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., 33â¯% 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.
Assuntos
Portadores de Fármacos , Nanopartículas , Fármacos Neuroprotetores , Soroalbumina Bovina , Vitamina B 12 , Animais , Vitamina B 12/análogos & derivados , Vitamina B 12/química , Vitamina B 12/farmacologia , Soroalbumina Bovina/química , Nanopartículas/química , Fármacos Neuroprotetores/química , Fármacos Neuroprotetores/farmacologia , Portadores de Fármacos/química , Ratos , Masculino , Ratos Wistar , Bovinos , Convulsões/tratamento farmacológico , Convulsões/prevenção & controleRESUMO
Folate and vitamin B12 (cobalamin) are essential for growth and development. This cross-sectional study aims to describe folate and vitamin B12 status according to infant age and breastfeeding practices in Norwegian infants. Infants aged 0-12 months (n = 125) were recruited through public health clinics. We registered breastfeeding status and measured serum concentrations of folate, cobalamin, total homocysteine (tHcy), and methylmalonic acid (MMA). The associations between infant age, breastfeeding, and biomarker concentrations were estimated in regression models. The mean (SD) age was 24 (16) weeks, and 42% were exclusively breastfed, 38% were partially breastfed, and 21% were weaned. Overall, median (IQR) folate, cobalamin, tHcy, and MMA concentrations were 47 (35-66) nmol/L, 250 (178-368) pmol/L, 6.99 (5.69-9.27) µmol/L, and 0.35 (0.24-0.83) µmol/L, respectively. None of the infants were folate deficient, 15% were vitamin B12 deficient (< 148 pmol/L), and 23% had low vitamin B12 status (148-221 pmol/L). Elevated tHcy (> 6.5 µmol/L) and MMA (> 0.26 µmol/L) were found in 62% and 69% of the infants, respectively. Compared to weaned, exclusively or partially breastfed infants were younger and had 46% higher tHcy concentrations (P < 0.001), in addition to 47% and 39% lower cobalamin concentrations (P < 0.001), respectively. However, the observed biomarker concentrations appeared to be independent of infant age. In conclusion, low vitamin B12 status was prevalent and appeared to be more common in the younger exclusively breastfed compared to older weaned infants. The implications of low vitamin B12 status in infancy are unknown and require further investigation.
Assuntos
Biomarcadores , Aleitamento Materno , Ácido Fólico , Homocisteína , Ácido Metilmalônico , Deficiência de Vitamina B 12 , Vitamina B 12 , Humanos , Vitamina B 12/sangue , Ácido Fólico/sangue , Estudos Transversais , Noruega , Lactente , Feminino , Biomarcadores/sangue , Homocisteína/sangue , Ácido Metilmalônico/sangue , Masculino , Deficiência de Vitamina B 12/sangue , Deficiência de Vitamina B 12/epidemiologia , Recém-Nascido , Estado Nutricional , Deficiência de Ácido Fólico/epidemiologia , Deficiência de Ácido Fólico/sangueRESUMO
BACKGROUND: No prospective study has evaluated the efficacy of oral supplementation with cobalamin in hypocobalaminemic cats. OBJECTIVES: To investigate the efficacy of oral or SC supplementation with cyanocobalamin in normalizing serum cobalamin and methylmalonic acid (MMA) concentrations in hypocobalaminemic cats with chronic gastrointestinal disease (CGID) or exocrine pancreatic insufficiency (EPI). ANIMALS: Forty-eight client-owned hypocobalaminemic (<290 ng/L) cats with normal or abnormally high serum MMA concentrations. METHODS: This study was conducted based on the prospective randomized clinical trial method. Cats with CGID or EPI were randomly assigned to 2 groups that received either oral or SC supplementation with cobalamin (250 µg/cat) for 12 and 10 weeks, respectively, in addition to other medical and dietary interventions. Each cat was evaluated 3 times (baseline, 6-week postsupplementation, and 1-week postcompletion) by measuring serum cobalamin and MMA concentrations. RESULTS: In cats with CGID or EPI, cobalamin concentrations were normalized in all cats that received either oral or SC supplementation (mean 100% [95% CI: 80.6%-100%] in both groups in cats with CGID and 100% [67.6%-100%] in both groups in cats with EPI). Among 37 cats with elevated MMA concentrations at baseline (21 cats with CGID and 16 cats with EPI), MMA concentrations were normalized in most cats with CGID (70% in oral and 82% in SC group) or EPI (88% in both groups). CONCLUSIONS AND CLINICAL IMPORTANCE: In hypocobalaminemic cats with CGID or EPI, in conjunction with other medical and dietary interventions, both oral and SC supplementation are effective at normalizing serum cobalamin and MMA concentrations.
Assuntos
Doenças do Gato , Insuficiência Pancreática Exócrina , Gastroenteropatias , Ácido Metilmalônico , Vitamina B 12 , Animais , Gatos , Doenças do Gato/tratamento farmacológico , Doenças do Gato/sangue , Vitamina B 12/administração & dosagem , Vitamina B 12/sangue , Vitamina B 12/uso terapêutico , Masculino , Feminino , Administração Oral , Insuficiência Pancreática Exócrina/veterinária , Insuficiência Pancreática Exócrina/tratamento farmacológico , Insuficiência Pancreática Exócrina/sangue , Gastroenteropatias/veterinária , Gastroenteropatias/tratamento farmacológico , Ácido Metilmalônico/sangue , Deficiência de Vitamina B 12/veterinária , Deficiência de Vitamina B 12/tratamento farmacológico , Estudos Prospectivos , Doença Crônica/veterinária , Injeções Subcutâneas/veterináriaRESUMO
AIM: To investigate the efficacy of Palmitoylethanolamide (PEA, 300 mg), Superoxide Dismutase (SOD, 70 UI), Alpha Lipoic Acid (ALA, 300 mg), vitamins B6 (1.5 mg), B1 (1.1 mg), B12 (2.5 mcg), E (7.5 mg), nicotinamide (9 mg), and minerals (Mg 30 mg, Zn 2.5 mg) in one tablet in people with Diabetic Neuropathy (DN). PATIENTS-METHODS: In the present pilot study, 73 people (age 63.0 ± 9.9 years, 37 women) with type 2 Diabetes Mellitus (DMT2) (duration 17.5 ± 7.3 years) and DN were randomly assigned to receive either the combination of ten elements (2 tablets/24 h) in the active group (n = 36) or the placebo (n = 37) for 6 months. We used the Michigan Neuropathy Screening Instrument Questionnaire and Examination (MNSIQ and MNSIE), measured vibration perception threshold (VPT) with biothesiometer, and Cardiovascular Autonomic Reflex Tests (CARTs). Nerve function was assessed by DPN Check [sural nerve conduction velocity (SNCV) and amplitude (SNAP)]. Sudomotor function was assessed with SUDOSCAN, which measures electrochemical skin conductance in hands and feet (ESCH and ESCF). Pain score (PS) was assessed with Pain DETECT questionnaire. Quality of life was assessed by questionnaire. RESULTS: In the active group, there was a large improvement of pain (PS from 20.9 to 13.9, p < 0.001). There was also a significant improvement of vitamin B12 (B12) levels, MNSIQ, SNCV, VPT, and ESCF (222.1 vs. 576.3 pg/ mL, p < 0.001; 6.1 vs. 5.9, p = 0.017; 28.8 vs. 30.4, p = 0.001; 32.1 vs. 26.7, p = 0.001; and 72.2 vs. 74.8, p < 0.001 respectively). In the placebo group, neither pain (21.6 vs. 21.7, p = 0.870) or any other aforementioned parameters changed significantly, and MNSIE worsened (2.9 vs. 3.4, p < 0.001). As a result, changes from baseline to follow-up in pain, B12 levels, VPT, and MNSIQ differed significantly between the two groups (p < 0.001, 0.025, 0.009, and <0.001, respectively). CARTs, SNAP, ESCH did not significantly change in either of the two groups. CONCLUSIONS: The combination of the ten elements in one tablet for 6 months at a daily dose of two tablets in people with DN significantly improves pain, vibration perception threshold, and B12 levels.
Assuntos
Amidas , Neuropatias Diabéticas , Etanolaminas , Niacinamida , Ácidos Palmíticos , Superóxido Dismutase , Ácido Tióctico , Vitamina B 12 , Vitamina B 6 , Humanos , Pessoa de Meia-Idade , Feminino , Neuropatias Diabéticas/tratamento farmacológico , Masculino , Idoso , Vitamina B 12/administração & dosagem , Ácido Tióctico/administração & dosagem , Projetos Piloto , Vitamina B 6/administração & dosagem , Ácidos Palmíticos/administração & dosagem , Etanolaminas/administração & dosagem , Niacinamida/administração & dosagem , Niacinamida/uso terapêutico , Amidas/administração & dosagem , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/complicações , Zinco/administração & dosagem , Vitamina E/administração & dosagem , Método Duplo-Cego , Tiamina/administração & dosagem , Resultado do Tratamento , Suplementos NutricionaisRESUMO
Background: Celiac disease is a chronic small intestinal immune-mediated enteropathy precipitated by exposure to dietary gluten, affecting approximately 1% of the global population and two million Americans. An increasing number of studies have identified a link between celiac disease and adverse maternal and fetal outcomes during pregnancy and after birth. Additionally, both celiac disease and pregnancy are associated with an increased risk for nutrient deficiencies, specifically vitamin B12 and folate. Methods: This review examines the current literature related to the folate trap and vitamin B12 deficiency in patients with celiac disease and pregnant women independently and provides rationale for future research to explore the relationship between the folate-to-12 ratio in pregnant women with celiac disease. Results: Deficiencies in vitamin B12 are linked with several negative maternal and fetal health outcomes including pre-eclampsia, gestational diabetes, spontaneous abortion/miscarriage, preterm birth, neural tube defects, intrauterine growth restriction, and low gestational age and birthweight. Conclusions: Folic acid supplementation is widely recommended during pregnancy, but complementary vitamin B12 supplementation is not standard. Physicians should consider celiac disease screening during pregnancy as well as vitamin B12 supplementation.
Assuntos
Doença Celíaca , Suplementos Nutricionais , Ácido Fólico , Complicações na Gravidez , Resultado da Gravidez , Deficiência de Vitamina B 12 , Vitamina B 12 , Humanos , Gravidez , Feminino , Doença Celíaca/complicações , Deficiência de Vitamina B 12/complicações , Ácido Fólico/administração & dosagem , Vitamina B 12/administração & dosagemRESUMO
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).
Assuntos
Ácido Fólico , Homocisteína , Síndrome do Ovário Policístico , Vitamina B 12 , Humanos , Síndrome do Ovário Policístico/sangue , Ácido Fólico/sangue , Feminino , Vitamina B 12/sangue , Homocisteína/sangueRESUMO
Background: DATATOP was a study of early Parkinson's disease (PD) conducted in the 1980âs, before mandatory folic acid fortification in the United States. Our analysis of its baseline serum samples revealed a geometric mean vitamin B12 of 369âpg/mL and homocysteine (tHcy) of 9.5µmol/l. We also found that low B12 predicted greater worsening of ambulatory capacity (AC) and elevated tHcy (>15µmol/L) predicted greater declines in cognitive function. Objective: We sought to measure B12 and tHcy in contemporary trial participants with early PD who had not started dopaminergic treatment and to determine whether these analytes were associated with clinical progression. Methods: We measured B12 and tHcy from baseline and end-of-study blood samples from three recent clinical trials. Results: Baseline geometric mean B12 levels for these studies ranged from 484- 618âpg/ml and for tHcy ranged from 7.4- 10µmol/L. Use of B12-containing supplements ranged from 41- 61%, and those taking supplements had higher B12 and lower tHcy. Those who began levodopa, but were not taking B12-supplements, had greater end-of-study tHcy. There was no association of baseline tHcyâ>â15µmol/L with annualized change in Montreal Cognitive Assessment and no association of baseline B12 tertiles with change in AC. Conclusions: In these longitudinal trials, B12 levels were higher than for DATATOP, due in large part to increased B12-supplement intake, while tHcy levels were similar. Initiation of levodopa was associated with increases of tHcy in those not taking a B12-containing supplement. These smaller studies did not replicate prior findings of low B12 and elevated tHcy with features of progression, possibly due to higher baseline B12.
Assuntos
Homocisteína , Doença de Parkinson , Vitamina B 12 , Humanos , Vitamina B 12/sangue , Homocisteína/sangue , Masculino , Feminino , Idoso , Doença de Parkinson/sangue , Doença de Parkinson/tratamento farmacológico , Pessoa de Meia-Idade , Progressão da Doença , Antiparkinsonianos/uso terapêutico , Levodopa/administração & dosagem , Levodopa/farmacologia , Suplementos Nutricionais , Disfunção Cognitiva/sangue , Disfunção Cognitiva/etiologia , Disfunção Cognitiva/tratamento farmacológicoRESUMO
Methylcobalamin (MBL) is a vitamin B12 coenzyme and is effective for treating peripheral neuropathies. Little is known about pharmacokinetics (PK) of MBL in animals, we have developed a simple assay for MBL by using only 0.01 mL of plasma for PK of MBL in rats. Under minimal light exposure (<5 lx), MBL was extracted by a simple protein precipitation using methanol and detected by liquid chromatography with tandem mass spectrometry. MBL in rat plasma at 20-10,000 ng/mL was quantified using only 0.01 mL of plasma. Relative error and relative standard deviation met the acceptance criteria in reproducibility assessments, indicating the robustness of the assay. PK of MBL was evaluated after intravenous, intramuscular, and subcutaneous administration. PK of MBL was dose proportional at 5-20 mg/kg in both intramuscular and subcutaneous administrations. Bioavailability after the two dosing routes was complete (ca. 100 %). The incurred sample reanalysis also supported that the assay is robust. The established assay was successfully applied to PK studies in rats to find that MBL showed high bioavailability after intramuscular and subcutaneous administrations.
Assuntos
Ratos Sprague-Dawley , Espectrometria de Massas em Tandem , Vitamina B 12 , Animais , Espectrometria de Massas em Tandem/métodos , Ratos , Masculino , Vitamina B 12/farmacocinética , Vitamina B 12/sangue , Vitamina B 12/administração & dosagem , Vitamina B 12/análogos & derivados , Cromatografia Líquida/métodos , Reprodutibilidade dos Testes , Disponibilidade Biológica , Injeções Intramusculares , Injeções Subcutâneas , Relação Dose-Resposta a Droga , Espectrometria de Massa com Cromatografia LíquidaRESUMO
The goal is to provide foundational data that could spearhead more extensive, prospective research into understanding the influences of micronutrient levels on the nocturnal patterns of hypertension, possibly aiding in identifying potential therapeutic strategies to reduce cardiovascular risk in this demographic. The research employed a retrospective design to analyze the micronutrient levels, including ferritin, folic acid, vitamin B12, and vitamin D, in a limited sample size from a single hospital. However, it is worth noting that the study did not scrutinize other potentially relevant micronutrients and biomarkers and lacked information on potential confounding factors such as lifestyle and dietary habits, physical activity levels, and specific details on antihypertensive medications used. The preliminary findings highlight a significant difference in ferritin levels between dipper and non-dipper groups, indicating a potential role in the development of non-dipper hypertension. Surprisingly, no notable difference was observed in vitamin D levels between the groups. The study underscores the increasing prevalence of hypertension and micronutrient deficiencies as age progresses. Despite its limitations, including limited sample size and potential influences from unaccounted variables, the study hints at a potential relationship between micronutrient levels and non-dipper hypertension. It emphasizes the necessity for larger scale, prospective research to delve deeper into the nature of this relationship, potentially fostering new therapeutic approaches in cardiovascular risk management within the elderly population.
Assuntos
Hipertensão , Micronutrientes , Vitamina D , Humanos , Hipertensão/epidemiologia , Estudos Retrospectivos , Idoso , Micronutrientes/sangue , Masculino , Feminino , Vitamina D/sangue , Ácido Fólico/sangue , Ferritinas/sangue , Vitamina B 12/sangue , Pressão Sanguínea/fisiologia , Idoso de 80 Anos ou mais , Pessoa de Meia-Idade , Ritmo Circadiano/fisiologiaRESUMO
Deficiency in vitamins B9 and B12 are common in general practice, due to their high prevalence in the population, especially among elderly patients. This article will present the clinical manifestations of vitamin B9 and B12 deficiencies, which can sometimes be insidious. We will discuss screening strategies, which are based on the presence of compatible symptoms as well as risk factors for deficiency. The choice of administration route for substitution depends both on severity and etiology; but the oral route has demonstrated similar effectiveness compared to intramuscular administration.
Il est courant de rencontrer des déficits en vitamines B9 et B12 en consultation de médecine de premier recours, en raison de leurs prévalences élevées dans la population générale, surtout chez les patients âgés. Cet article présente les manifestations cliniques de carences en vitamines B9 et B12, qui peuvent parfois être insidieuses et discute des stratégies de dépistage, qui se basent sur la présence de symptômes compatibles ainsi que de facteurs de risque de carence. Concernant la substitution, le choix de la voie d'administration se fait selon la sévérité et l'étiologie ; mais la forme orale a démontré une efficacité similaire à l'administration intramusculaire.