Methyl-donor supplementation in women with systemic lupus erythematosus with different nutritional status: the protocol for a randomised, double-blind, placebo-controlled trial.

INTRODUCTION: DNA hypomethylation in patients with systemic lupus erythematosus (SLE) has been recently documented in the literature. Low levels of DNA methylation have been observed globally and in genes associated with immune and inflammatory pathways in SLE's CD4+T lymphocytes. Given that certain micronutrients can either donate methyl groups within one-carbon metabolism pathways or serve as cofactors for enzymes involved in the DNA methylation process, this randomised, double-blind, placebo-controlled trial aims to investigate whether a 3-month supplementation of folic acid and vitamin B12 will modulate the DNA methylation profile in subcutaneous adipose tissue (primary outcome) of women with SLE and normal weight or excess body weight. As secondary objectives, we will assess gene expression, telomere length and phenotypic characteristics (ie, clinical parameters, body weight and composition, abdominal circumference, food intake and disordered eating attitude, physical activity, lipid profile, serum concentrations of leptin, adiponectin, and cytokines). METHODS AND ANALYSIS: Patients will be classified according to their nutritional status by body mass index in normal weight or excess body weight. Subsequently, patients in each group will be randomly assigned to either a placebo or an intervention group (folic acid (400 mcg) and vitamin B12 (2000 mcg) supplementation). Endpoint evaluations will be conducted using both intention-to-treat and per-protocol analyses. This study has the potential to design new personalised nutritional approaches as adjunctive therapy for patients with SLE. ETHICS AND DISSEMINATION: This study has been reviewed and approved by the Ethical Committee from Clinical Hospital of the School of Medicine of the University of Sao Paulo, Brazil (CAAE.: 47317521.8.0000.0068). TRIAL REGISTRATION NUMBER: NCT05097365 (first version).

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).

A case series of low-level laser therapy treatment in patients with peripheral facial palsy.

BACKGROUND: Peripheral Facial Palsy (PFP) is a facial paralysis with various etiologies, including idiopathic causes (Bell's palsy), infections, trauma, and genetic factors. Traditional treatments involve antiviral medications, corticosteroids, and physiotherapy. However, new therapies, such as Low-Level Laser Therapy (LLLT), are emerging with promising results. METHODS: This case series reports on two patients with PFP treated with LLLT combined with Vitamin B1, B6, and B12 supplementation. The first case involved a 52-year-old female with PFP due to a viral infection. The second case was a 33-year-old male who developed PFP following a traumatic brain injury. Both patients received LLLT sessions every two weeks, targeting 10 points along the facial nerve pathway from the facial notch across the face. The laser device used was the Theraphy EC (DMC, Sao Carlos, SP, Brazil), with each point receiving 4 Joules of energy applied perpendicular to the skin after cleaning the face with water and soap to remove lipids that could interfere. The administration of Vitamin B was done using NEUROBIONTA tablets (Vitamin B1 + Vitamin B6 + Vitamin B12; Procter & Gamble, Santiago, Chile) with one tablet taken daily for 30 days. RESULTS: After six to seven sessions, both patients showed significant improvement in facial muscle function and overall facial symmetry. In the first case, improvements were noted in muscle tonicity and facial movements, with the patient reporting reduced facial disfigurement. In the second case, notable recovery in facial mobility and symmetry was observed, with the patient experiencing decreased paresthesia and restored muscle functionality. CONCLUSION: These findings suggest that LLLT, combined with Vitamin B1, B6, and B12 supplementation, may effectively improve facial muscle function and symmetry in PFP patients. The non-invasive nature and ease of application make LLLT a viable option for PFP treatment. Further studies with larger sample sizes and standardized protocols are necessary to confirm these results and establish LLLT as a standard treatment for PFP.

A Randomized Control Trial of Dexketoprofen/Vitamin B (Thiamine, Pyridoxine and Cyanocobalamin) Fixed-Dose Combination in Post-Traumatic Grade I-II Cervical Sprains.

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

Folate and Vitamin B12 Levels in Chilean Women with PCOS and Their Association with Metabolic Outcomes.

Polycystic ovary syndrome (PCOS) is a common endocrine disorder that affects women of reproductive age. Many women with PCOS have been found to have an unbalanced diet and deficiencies in essential nutrients. This study aimed to assess the levels of folate and vitamin B12 (B12) and their relationship with metabolic factors in women with PCOS. Anthropometric, clinical, and genetic analyses were conducted to evaluate markers related to one-carbon metabolism in women with PCOS and in a control group. The PCOS group had a higher BMI and HOMA-IR (1.7 vs. 3.1; p < 0.0001). HDL cholesterol levels were 23% lower and triglyceride levels were 74% higher in women with PCOS. Although there were no significant differences in folate and B12 levels between the PCOS and control groups, over 60% of women with PCOS had low B12 levels (<300 pg/mL) and high homocysteine levels. In addition, the MTHFR A1298C and C677T polymorphisms were not associated with PCOS. Moreover, erythrocyte folate levels were positively correlated with fasting glucose, triglycerides, and free androgen index, and negatively correlated with SHBG and LH levels. These results suggest that B vitamins may be associated with the metabolic phenotype in PCOS. This study emphasizes the potential link between folate, vitamin B12, and metabolic and hormonal outcomes in women with PCOS.

Folate and vitamin B12 related to homocysteine and DNA damage in female university students / Folato e vitamina B12 relacionados com homocisteína e danos no DNA em estudantes universitárias / Folato y vitamina B12 relacionados con homocisteína y daño en el ADN en estudiantes universitarias

Background and Objectives: It is not clear whether the increase in nutrition students' knowledge is associated with healthier eating behavior and fewer micronutrient deficiencies that can cause DNA damage. Deficiency in some vitamins can be a risk factor for increased homocysteine (Hcy) levels, a marker of cardiovascular risk. Therefore, this study aimed to verify whether dietary and serum folate and vitamin B12 are associated with Hcy levels and DNA damage in female university students. Methods: A cross-sectional study was conducted with female university students from southern Brazil. Folate, vitamin B12, and Hcy levels were determined in their diet or serum. DNA damage levels were assessed by the alkaline comet assay (index and frequency) and the buccal micronucleus assay (micronuclei frequency and binucleated cells frequency). Results: Correlation analyses did not show an association between Hcy levels and dietary or serum folate and vitamin B12 consumption. Dietary folate and vitamin B12 were associated with the index and frequency of damages; however, only serum folate was negatively associated with the index and frequency of damages. Additionally, the frequency of binucleated cells was negatively associated with dietary vitamin B12 and positively associated with serum levels. Serum folate was negatively associated with the frequency of micronuclei. Hcy levels were associated with the index and frequency of damages. Conclusion: These findings strengthen the role of healthier dietary patterns with adequate micronutrients as a preventive strategy to reduce the risk of cardiovascular diseases. This approach should play a pivotal role in shaping health policies and advocating for appropriate food choices.(AU)

Justificativa e Objetivos: Não está claro se o aumento do conhecimento dos estudantes de nutrição está associado a um comportamento alimentar mais saudável, com menores deficiências de micronutrientes que podem induzir danos no DNA. A deficiência de algumas vitaminas pode ser um fator de risco para o aumento dos níveis de homocisteína (Hcy), um marcador de risco cardiovascular. Portanto, este estudo verificou se folato e vitamina B12 dietético e sérico estão associados aos níveis de Hcy e danos no DNA em estudantes universitárias. Métodos: Estudo transversal com universitárias do sul do Brasil. Determinou-se folato, vitamina B12 e Hcy dietético e séricos. Os níveis de danos no DNA foram avaliados pelo ensaio do cometa alcalino (índice e frequência) e pelo ensaio de micronúcleos bucais (frequência de micronúcleos e células binucleadas). Resultados: Análises de correlação não mostraram associação entre os níveis de Hcy com o consumo de folato e vitamina B12 dietético ou sérico. Folato e vitamina B12 dietéticos associou-se ao índice e frequência de danos, entretanto, somente folato sérico associou-se negativamente ao índice e frequência de danos. Ainda, a frequência de células binucleadas estava negativamente associada à vitamina B12 da dieta e positivamente associada aos níveis séricos. Folato sérico associou-se negativamente à frequência de micronúcleos. Os níveis de Hcy associou-se ao índice e frequência de danos. Conclusão: Esses achados fortalecem o papel de padrões alimentares mais saudáveis com micronutrientes adequados como estratégia preventiva visando a redução do risco de doenças cardiovasculares. Esta abordagem deve desempenhar um papel fundamental na formulação de políticas de saúde e na defesa de escolhas alimentares apropriadas.(AU)

Justificación y Objetivos: No está claro si el aumento del conocimiento de estudiantes de nutrición está asociado con un comportamiento alimentario más saludable, con menores deficiencias de micronutrientes que puedan inducir daños en ADN. La deficiencia de algunas vitaminas puede ser un factor de riesgo para el aumento de los niveles de homocisteína (Hcy), marcador de riesgo cardiovascular. Consiguiente, este estudio verificó si folato y vitamina B12 dietéticos y séricos están asociados con niveles de Hcy y daños en el ADN en estudiantes universitarias. Métodos: Estudio transversal con universitarias del sur de Brasil. Se determinaron folato, vitamina B12 y Hcy dietéticos y séricos. Los niveles de daño en el ADN se evaluaron por ensayo del cometa alcalino (índice y frecuencia) y el ensayo de micronúcleos bucales (frecuencia de micronúcleos y células binucleadas). Resultados: Los análisis de correlación no mostraron asociación entre los niveles de Hcy con folato y vitamina B12 dietéticos y séricos. Folato y vitamina B12 dietéticos se asociaron con índice y frecuencia de daños, pero, solo folato sérico se asoció negativamente con índice y frecuencia de daños. Además, la frecuencia de células binucleadas estaba negativamente asociada con la vitamina B12 de la dieta y positivamente asociada con los niveles séricos. Folato sérico se asoció negativamente con la frecuencia de micronúcleos. Los niveles de Hcy se asociaron con índice y frecuencia de daños. Conclusión: Estos hallazgos refuerzan el papel de patrones alimentarios más saludables con micronutrientes adecuados como estrategia preventiva para reducir el riesgo de enfermedades cardiovasculares. Este enfoque debería desempeñar un papel fundamental en la elaboración de políticas de salud y en la promoción de elecciones alimenticias apropiadas.(AU)

Homocystein, Vitamin B12 and Folic Acid as Screening Biomarkers in Early Diagnosis and Gastric Cancer Monitoring.

Gastric cancer has been demonstrating a reduction in the number of cases over the past decades, largely attributed to advancements in public health practices and increased accessibility to educational initiatives for the general population. Nevertheless, it persists as the third leading cause of mortality globally among both men and women. These fatalities are typically associated with delayed disease detection. The current study assessed the levels of homocysteine, vitamin B12, and folic acid as a means of establishing a screening biomarker profile that could be integrated into routine testing protocols to facilitate swift diagnosis of the illness. A total of 207 control subjects and 207 individuals with gastric cancer were scrutinized, with biochemical measurements conducted using chemiluminescence for homocysteine, folic acid, and vitamin B12. The two groups were matched based on age, tumor location, subtype, tumor classification, presence of Epstein-Barr Virus infection (EBV), and Helicobacter pylori (H. pylori). Significant statistical variances were identified in the mean levels of the triad of substances among cancer patients when compared to the control group for all corresponding variables. In conclusion, our study indicated that analyzing the triad of homocysteine, vitamin B12, and folic acid holds diagnostic value for gastric cancer and could potentially serve as an effective screening marker for this type of cancer in the future.

A 12-Week Ballroom Dance Training Improves Physical Fitness Performance More Than Walking Training in Older Women, Regardless of Vitamin B12 or D Adequacy.

AIM: This study aimed to compare the effects of Ballroom Dancing (BD) versus Walking Training (WT) on the physical fitness performance in physically independent older women with adequate or inadequate levels of vitamins B12 and D. METHODS: Forty-three sedentary women aged 68.5 ± 6.5 years, were allocated to the BD (n = 23) or WT (n = 20) groups. They took part in a 12-week intervention, performed 3 times a week, for about 50 minutes with moderate effort intensity. Data were collected through Short Physical Performance Battery (SPPB), 6 minutes Walk Test (6MWT), Hand Grip Test (HGT), Isokinetic tests for lower limbs and blood tests to detect serum levels of vitamins B12 and D. RESULTS: The BD group performed better after the intervention in relation to the WT in the Sit and Stand Test (SST) (BD pre = 3.1 score vs post = 3.8 score; WT pre = 2.8 score vs post = 3.4 score; P = .02) and in the Peak Torque 180° extension (PKTOQ 180° extension) (BD pre = 56.7 Nm vs post = 61.2 Nm, WT pre = 56.7 Nm vs post = 56.1; P < .01). CONCLUSION: A time effect was observed in all other variables, with the exception of HGT. Both interventions improved physical fitness performance, regardless of the adequacy of vitamins B12 and D, but the older women from BD obtained significant improvements in more variables than the WT.

New data supporting that early diagnosis and treatment are possible and necessary in intracellular cobalamin depletion: the case of transcobalamin II deficiency.

OBJECTIVES: Transcobalamin II (TC) promotes the cellular uptake of cobalamin (Cbl) through receptor-mediated endocytosis of the TC-cbl complex in peripheral tissues. TC deficiency is a rare disorder that causes intracellular Cbl depletion. It presents in early infancy with a failure to thrive, diarrhea, anemia, agammaglobulinemia, and pancytopenia. Data from five TC-deficient patients including clinical, biochemical, and molecular findings, as well as long-term outcomes, were collected. CASE PRESENTATION: Mutation analysis revealed one unreported pathogenic variant in the TCN2 gene. One patient had exocrine pancreatic insufficiency. We conducted a retrospective analysis of C3 and C3/C2 from dried blood samples, as this is implemented for newborn screening (NBS). We detected a marked increase in the C3/C2 ratio in two samples. Treatment was based on parenteral Cbl. Three patients treated before six months of age had an initial favorable outcome, whereas the two treated later or inadequately had neurological impairment. CONCLUSIONS: This is the first report of Argentinean patients with TC deficiency that detected a new variant in TCN2. NBS may be a tool for the early detection of TC deficiency. This data emphasizes that TC deficiency is a severe disorder that requires early detection and long-term, aggressive therapy. Accurate diagnosis is imperative, because early detection and treatment can be life-saving.

Correlación entre Vitamina B12 y presión arterial en adultos / Correlation between Vitamin B12 and blood pressure in adults

Introducción. La vitamina B12 incidiría sobre la presión arterial mediante mecanismos hormonales y metabólicos. Objetivo. Analizar la relación entre las concentraciones de vitamina B12 y la presión arterial en adultos. Materiales y Métodos. Estudio observacional, analítico, retrospectivo y transversal, proveniente de una base de datos abierta conformada por 4154 personas de una comunidad mexicana atendida en un establecimiento de salud. Las variables fueron: sexo, vitamina B12 y presión arterial sistólica. Se utilizó las pruebas Ji-cuadrado y prueba t de student. Resultados.los promedios de vitamina B12 fueron menores en presencia de presión arterial igual o mayor a 130 mmHg (hombres:217,12 pg/ml; mujeres204,51 pg/ml) respecto a cuándo se comparó con niveles de presión arterial sistólica entre 90 a 129 mmHg (hombres; 266,98 pg/ml; mujeres: 205,18 og/ml). La correlación entre vitamina B12 y presión arterial fue baja y negativa en hombres (Rho=-0,022; p=0,018), mujeres (Rho=-0,182; p<0,001) y en ambos grupos en conjunto (Rho=-0,171; p<0,001).Conclusión. Los adultos hipertensos tienen menores promedios de vitamina B12 que los normotensos. Asimismo, la vitamina B12 se correlaciona de forma débil y negativa con la presión arterial. Los niveles normales de vitamina B12 con tendencia hacia los limites bajos podrían ser uno de los muchos factores que inciden en la fisiopatología temprana de la hipertensión arterial. Palabras clave: vitamina B 12; presión arterial; estudio observacional; modelos lineales; correlación de datos

Introduction. Vitamin B12 would affect blood pressure through hormonal and metabolic mechanisms.Objective. To analyze the relationship between vitamin B12 concentrations and blood pressure in adults.Materials and Methods. Observational, analytical, retrospective and cross-sectional study, from an open database made up of 4,154 people from a Mexican community served in a health facility. The variables were: sex, vitamin B12 and systolic blood pressure. The Chi-square test and student's t test were used.Results. the averages of vitamin B12 were lower in the presence of blood pressure equal to or greater than 130 mmHg (men: 217.12 pg/ml; women 204.51 pg/ml) compared to when it was compared with systolic blood pressure levels between 90 at 129 mmHg (men; 266.98 pg/ml; women: 205.18 og/ml). The correlation between vitamin B12 and blood pressure was low and negative in men (Rho=-0.022; p=0.018), women (Rho=-0.182; p<0.001) and in both groups together (Rho=-0.171; p< 0.001). Conclusion. Hypertensive adults have lower averages of vitamin B12 than normotensive adults. Likewise, vitamin B12 is weakly and negatively correlated with blood pressure. Normal levels of vitamin B12 with a tendency towards low limits could be one of the many factors that influence the early pathophysiology of arterial hypertension. Key words:vitamin B12; arterial pressure; observational study; linear models; correlation of data

Vitaminas B neurotrópicas y neuropatía periférica: estado del arte y acuerdo de expertos / Neurotropic B vitamins and peripheral neuropathy: State of the art and agreement of experts

Propósito: La neuropatía periférica tiene un espectro clínico inespecífico y multifactorial, con frecuente subdiagnóstico y terapéutica de eficacia variable. Existe una heterogénea prescripción de vitaminas B, las cuales pueden desempeñar un rol importante en el manejo de diferentes neuropatías; sin embargo, en Colombia no existen guías clínicas al respecto. El propósito de este trabajo es orientar en el reconocimiento temprano de las neuropatías periféricas y generar recomendaciones sobre el uso adecuado de vitaminas B neurotrópicas. Descripción de la metodología: Acuerdo de expertos sobre la neuropatía periférica y el rol terapéutico de las vitaminas B con énfasis en la epidemiología en Colombia, diagnóstico y tratamiento. Contenidos: En Colombia, la prevalencia de neuropatía periférica se estima cercana al 10 %, sin embargo, no hay datos recientes. Dentro de las etiologías más frecuentes se encuentran la neuropatía diabética, infecciosa, inflamatoria, carenciales, toxica y farmacológica. Se recomiendan las siguientes herramientas de tamizaje en población de riesgo: DN4, MNSI, test de monofilamento, test de vibración y valoración de reflejos. Las vitaminas B1, B6 y B12 son seguras, accesibles y pueden ser eficaces en neuropatía periférica, incluso cuando el déficit no ha sido demostrado, pero con requerimientos particulares en su administración conjunta. Conclusiones: Las neuropatías periféricas son un reto diagnóstico y terapéutico que requiere la identificación oportuna para el tratamiento de la etiología subyacente y el control de síntomas. El uso de vitaminas B neurotrópicas es efectivo y seguro en neuropatía periférica carencial, y también parece ser eficaz en el manejo de neuropatías periféricas de diferentes etiologías.

Purpose: Peripheral neuropathy has a nonspecific and multifactorial clinical spectrum, with frequent underdiagnosis and therapeutics of variable efficacy. There is a high but heterogeneous prescription of B vitamins, which can play an important role in the management of different neuropathies; however, in Colombia there are no clinical guidelines in this regard. The purpose of this article is to guide the early recognition of peripheral neuropathy and generate recommendations on the proper use of neurotropic B vitamins. Description of the methodology: Expert agreement on peripheral neuropathy and the therapeutic role of B vitamins with emphasis on epidemiology in Colombia, diagnosis and treatment. Contents: In Colombia, there are no recent data to estimate the prevalence of peripheral neuropathy; the main etiologies are: diabetes mellitus, nutritional deficiencies, herpes zoster and neuropathies due to chemotherapy. Given risk factors in the anamnesis, the use of DN4, MNSI, monofilament test, vibration test and assessment of reflexes is recommended. Vitamins B1, B6, and B12 are safe and can be effective in peripheral neuropathy, even when the deficit has not been demonstrated, but with special requirements in their joint administration. Conclusions: peripheral neuropathies are a diagnostic and therapeutic challenge, and require timely identification, for the treatment of the underlying etiology and symptom control. The use of neurotropic B vitamins is effective and safe in deficient peripheral neuropathy, and also appears to be effective in the management of peripheral neuropathies of different etiologies.

Effect of a combination of gliptin and metformin on serum vitamin B12, folic acid, and ferritin levels.

OBJECTIVE: The primary objective of this study was to explore the impact of metformin and metformin/gliptin combination therapy on the serum concentrations of vitamin B12, ferritin, and folic acid in individuals diagnosed with type 2 diabetes. METHODS: This study included 118 patients, classified into two groups: 59 patients using only metformin and 59 patients using a combination of metformin/gliptin. Among the latter group, 35 patients used vildagliptin/metformin, and 24 used sitagliptin/metformin. The study recorded the demographic data such as the age and gender of the patients, as well as their initial and 1-year follow-up blood parameters. RESULTS: Folic acid decreased significantly in the metformin group but not in the metformin/gliptin group. Vitamin B12 and ferritin decreased significantly in both groups. The decrease in vitamin B12 and ferritin was not significantly different between the two groups. The decrease in fasting plasma glucose was more significant in the metformin/gliptin group than in the metformin group. CONCLUSION: After 1 year, both groups taking metformin and metformin/gliptin showed low serum ferritin and vitamin B12 levels. Therefore, vitamin B12 levels in patients using these drugs should be closely monitored. Ferritin levels can be used to indicate whether glycemic control has been achieved.

Uncovering the neuroprotective effect of vitamin B12 in pneumococcal meningitis: insights into its pleiotropic mode of action at the transcriptional level.

Background: The interplay between bacterial virulence factors and the host innate immune response in pneumococcal meningitis (PM) can result in uncontrolled neuroinflammation, which is known to induce apoptotic death of progenitor cells and post-mitotic neurons in the hippocampal dentate gyrus, resulting in cognitive impairment. Vitamin B12 attenuates hippocampal damage and reduces the expression of some key inflammatory genes in PM, by acting as an epidrug that promotes DNA methylation, with increased production of S-adenosyl-methionine, the universal donor of methyl. Material and methods: Eleven-day-old rats were infected with S. pneumoniae via intracisternal injection and then administered either vitamin B12 or a placebo. After 24 hours of infection, the animals were euthanized, and apoptosis in the hippocampal dentate gyrus, microglia activation, and the inflammatory infiltrate were quantified in one brain hemisphere. The other hemisphere was used for RNA-Seq and RT-qPCR analysis. Results: In this study, adjuvant therapy with B12 was found to modulate the hippocampal transcriptional signature induced by PM in infant rats, mitigating the effects of the disease in canonical pathways related to the recognition of pathogens by immune cells, signaling via NF-kB, production of pro-inflammatory cytokines, migration of peripheral leukocytes into the central nervous system, and production of reactive species. Phenotypic analysis revealed that B12 effectively inhibited microglia activation in the hippocampus and reduced the inflammatory infiltrate in the central nervous system of the infected animals. These pleiotropic transcriptional effects of B12 that lead to neuroprotection are partly regulated by alterations in histone methylation markings. No adverse effects of B12 were predicted or observed, reinforcing the well-established safety profile of this epidrug. Conclusion: B12 effectively mitigates the impact of PM on pivotal neuroinflammatory pathways. This leads to reduced microglia activation and inflammatory infiltrate within the central nervous system, resulting in the attenuation of hippocampal damage. The anti-inflammatory and neuroprotective effects of B12 involve the modulation of histone markings in hippocampal neural cells.

Biological Pathways Associated with Vitamins in Autism Spectrum Disorder.

Autism spectrum disorder (ASD) is characterized by early-appearing social communication deficits, with genetic and environmental factors potentially playing a role in its etiology, which remains largely unknown. During pregnancy, certain deficiencies in critical nutrients are mainly associated with central nervous system impairment. The vitamin B9 (folate) is primarily related to one-carbon and methionine metabolism, participating in methyl donor generation. In addition, supplementation with folic acid (FA) is recommended by the World Health Organization (WHO) in the first three gestational months to prevent neural tube defects. Vitamin B12 is related to folate regeneration, converting it into an active form. Deficiencies in this vitamin have a negative impact on cognitive function and brain development since it is involved in myelin synthesis. Vitamin D is intimately associated with Ca2+ levels, acting in bone development and calcium-dependent signaling. This vitamin is associated with ASD at several levels since it has a relation with ASD genes and oxidative stress environment. This review carries the recent literature about the role of folate, vitamin B12, and vitamin D in ASD. In addition, we discuss the possible impact of nutrient deficiency or hypersupplementation during fetal development. On the other hand, we explore the biases of vitamin supplementation studies such as the loss of participants in retrospective studies, as well as multiple variants that are not considered in the conclusion, like dietary intake or auto-medication during pregnancy. In this regard, we aim to contribute to the discussion about the role of vitamins in ASD currency, but also in pregnancy and fetal development as well. Furthermore, stress during pregnancy can be an ASD predisposition, with cortisol as a regulator. In this view, we propose that cortisol is the bridge of susceptibility between vitamin disorders and ASD prevalence.

Vitamin B12, folate, and homocysteine in metabolic syndrome: a systematic review and meta-analysis.

Background & aims: Metabolic syndrome (MetS) is associated with life-threatening conditions. Several studies have reported an association of vitamin B12, folic acid, or homocysteine (Hcy) levels with MetS. This systematic review and meta-analysis assessed the association of vitamin B12, folic acid, and Hcy levels with MetS. Methods: PubMed, Scopus, Embase, Ovid/Medline, and Web of Science were searched up to February 13, 2023. Cross-sectional, case-control, or cohort studies were included. A random-effects model was performed using the DerSimonian and Laird method to estimate the between-study variance. Effect measures were expressed as odds ratios (OR) with their corresponding 95% confidence intervals (95% CI). Between-study heterogeneity was evaluated using Cochran's Q test and the I2 statistic. Results: Sixty-six articles (n = 87,988 patients) were included. Higher vitamin B12 levels were inversely associated with MetS (OR = 0.87; 95% CI: 0.81-0.93; p < 0.01; I2 = 90%). Higher Hcy levels were associated with MetS (OR = 1.19; 95% CI: 1.14-1.24; p < 0.01; I2 = 90%). Folate levels were not associated with MetS (OR = 0.83; 95% CI: 0.66-1.03; p = 0.09; I2 = 90%). Conclusion: Higher vitamin B12 levels were inversely associated with MetS, whereas higher Hcy levels were associated with MetS. Studies assessing the pathways underlying this association are required.

Flow cytometry-detected changes in megaloblastic anemia secondary to cobalamin deficiency.

Introduction: Megaloblastic anemias secondary to Vitamin B12 deficiency are a group of pathologies produced by defective nuclear DNA synthesis. Objective: To describe the maturation alterations found in hematopoietic precursors of the bone marrow in a series of patients with megaloblastic anemia. Methods: Were included patients attended at the Regional Hospital of Concepción with bone marrow samples sent for the study of cytopenia by flow cytometry whose final diagnosis was megaloblastic anemia. The immunophenotype was performed with CD45, CD34, CD117, HLA-DR, markers of neutrophil (CD13, CD11b, CD10, CD16) and/or erythroblast (CD105, CD71, CD36) maturation. Results: From the flow cytometry laboratory database, 8 patients with megaloblastic anemia were identified, and myelodysplastic syndromes (n=9) and normal or reactive bone marrow (n=10) were used as controls. 44% were men, with a median age of 58 years. Megaloblastic anemia was associated with a higher proportion of size and complexity of erythroid and myeloid progenitors compared to lymphocytes compared to controls. The total percentage of erythroblasts and the proportion of CD34+ myeloid cells associated with erythroid lineage was higher in megaloblastic anemia, associated with a maturation arrest in the CD105+ precursor stage (69% vs 19% and 23%, p<0.001). The heterogeneity of CD36 and CD71 in megaloblastic anemia was similar to myelodysplastic syndromes. Conclusions: Megaloblastic anemia produces a heterogeneous involvement of hematopoiesis, characterized by a greater size and cellular complexity of precursors of the neutrophil and erythroid series and a maturation arrest of the erythroblasts.

Introducción: Anemias megaloblásticas secundarias a la deficiencia de vitamina B12 son patologías producidas por una síntesis defectuosa del ADN nuclear. Objetivo: Describir las alteraciones madurativas encontradas en precursores hematopoyéticos de la médula ósea de una serie de pacientes con anemia megaloblástica. Métodos: Se incluyeron pacientes atendidos en el Hospital Regional de Concepción con muestras de médula ósea enviadas para estudio de citopenias por citometría de flujo cuyo diagnóstico fue anemia megaloblástica. El inmunofenotipo se realizó con CD45, CD34, CD117, HLA-DR, marcadores de maduración de serie de neutrófilo (CD13, CD11b, CD10, CD16) y/o eritroblasto (CD105, CD71, CD36). Resultados: Se identificaron 8 pacientes con anemia megaloblástica y como controles se utilizaron síndromes mielodisplásicos (n=9) y médula ósea normal o reactiva (n=10). El 44% eran hombres, con una mediana de edad de 58 años. La anemia megaloblástica se asoció con una mayor proporción de tamaño y complejidad de progenitores eritroides y mieloides con respecto de los linfocitos en comparación a los controles. El porcentaje total de eritroblastos y la proporción de células mieloides CD34+ comprometidas con el linaje eritroide fue mayor en anemia megaloblástica, asociado a una parada madurativa en la etapa de precursor CD105+ (69% vs 19% y 23%, p <0.001). La heterogeneidad de CD36 y CD71 en anemia megaloblástica fue similar a los síndromes mielodisplásicos. Conclusiones: la anemia megaloblástica produce una afectación heterogénea de la hematopoyesis, caracterizada por un mayor tamaño y complejidad celulares de precursores de la serie neutrófilo y eritroide y una detención madurativa de los eritroblastos.