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BACKGROUND: Vitamin B deficiencies are involved with several outcomes in fertility and pregnancy. In Brazil, the national prevalence rates of these micronutrient deficiencies in women of reproductive age were not known. This study aims to systematically identify, select, evaluate, analyze, and report the prevalence rates of vitamin B complex deficiencies in women of reproductive age in Brazil and identify variables that may modify the outcome rates. METHODS: A systematic review will be conducted guided by the following question: "What is the prevalence of vitamin B deficiencies in women of reproductive age in Brazil?". The studies will be identified and selected from a literature search using electronic databases, consultation with researchers/specialists, and reference lists of eligible studies and reviews on the topic. Major eligibility criteria include observational cross-sectional and cohort studies carried out in Brazil and performed in women 10-49 years old, or pregnant and lactating mothers, and investigated the deficiency of vitamin B complex by laboratory test. Two reviewers independently will perform the screening and selection of the studies, data extraction, and risk of bias assessment. For the data report, a narrative approach will be used to present the characteristics of the included studies and individual findings. A random meta-analysis model will be implemented to summarize the individual prevalence rates in a global value if the studies are sufficiently homogeneous. DISCUSSION: This study aims to identify the national and regional prevalence rates of vitamin B complex deficiencies in women of reproductive age; allow the policymakers discuss, plan, and implement public policies to screen; and prevent and/or treat these malnutrition conditions. This also aims to know the rates of nutritional deficiencies over the years, serving as an indirect indicator of the socioeconomic and dietary patterns of the population. Specifically for folate, this study allows to compare the prevalence rates of deficiency of this vitamin before and after the mandatory fortification of wheat and corn flours implemented since 2004 in Brazil, in this specific population. The evidence gathered may highlight the need for population-based studies to investigate the deficiency of these vitamins. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42020188474.

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Resumen La Diabetes Mellitus tipo 2 se ha convertido en un problema de salud pública en el mundo por su alta carga de morbimortalidad y costos por las complicaciones a corto y largo plazo. La Metformina es el antidiabético más comúnmente ordenado para el tratamiento por su costoefectividad y seguridad cardiovascular(1). Presentamos un paciente con sincope por anemia severa megaloblástica causada por déficit de Vitamina B 12 donde la única explicación fue consumo crónico de Metformina. Recibió manejo con Cianocobalamina y presentó recuperación de los parámetros eritrocitarios. Es importante llamar la atención en la monitorización periódica de los niveles de vitamina B 12 en esta población, sobretodo en pacientes que se presentan con síntomas de neuropatía periférica o anemia.

Abstract Type 2 Diabetes Mellitus has become a public health concern globally due to its high morbidity, mortality and costs caused by short and long-term complications. Metformin is the antidiabetic drug most frequently prescribed because its cost-effectiveness and cardiovascular safety. We present the case of a patient with syncope caused by a severe megaloblastic anemia associated to Vitamin B12 deficiency, in which the only possible cause found was the chronic use of Metformin. Patient received treatment with Cyanocobalamin and showed improvement in erythrocyte indices. It is relevant to highlight importance of the periodic monitoring of Vitamin B12 levels in this type of patients, especially in those presenting symptoms of peripheral neuropathy or anemia.

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BACKGROUND: Preeclampsia is a pregnancy-related pathological condition triggered by an abnormal placentation which produces endothelial dysfunction (ED). ED, in turn, is associated with an increase in homocysteine (hcy) and asymmetric dimethylarginine (ADMA); these molecules are also increased when some of the B-vitamins are deficient. It is unclear whether increases in hcy and ADMA during preeclampsia are the result of ED, or the consequence of a B-vitamin deficiency. OBJECTIVE: To evaluate hcy, ADMA, folic acid (FA), vitamin B6 and B2 concentrations in patients with preeclampsia. METHODS: In a cross-sectional design 19 patients with severe preeclamp- sia (preeclampsia) and 57 with normal pregnancy (no-preeclampsia), paired by gestational age and body mass index, were studied. Plasma hcy, ADMA, FA and vitamins B6 and B12 were determined. Non-parametric statistics was used for between-groups comparisons and regression analyses to evaluate interactions among molecules. RESULTS: 72% of women were vitamin B deficient, 40% were deficient of B12 and 4% of FA. Preeclamptic patients presented hcy and ADMA concentrations higher than no-preeclamptic ones. Inferential analyses demonstrated that: hcy and ADMA are increased during preeclampsia independently from vitamins blood concentration; that the risk for pre- eclampsia is associated with high hcy but not with vitamins deficiency; and that the ratio L-arginine:ADMA decreases the preeclampsia risk. CONCLUSION: In patients with preeclampsia, increases of hcy and ADMA are associated with ED, but not with deficiency of the vitamins involved in their metabolism.

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OBJECTIVE: To evaluate the usefulness of serial determinations of asymmetric dimethylarginine (ADMA) and homocysteine (Hcy) concentrations during pregnancy to predict pre-eclampsia, taking into account maternal obesity and B vitamin status. DESIGN: Longitudinal study. SETTING: Two obstetric referral hospitals. SAMPLE: Two hundred and fifty-two of 411 women invited to participate in the study. METHODS: The women made monthly visits from ≤20 weeks of gestation until delivery for measurements of plasma ADMA, Hcy, and vitamins B6 , B12, and folic acid, and for the recording of clinical information. MAIN OUTCOME MEASURE: Early elevations in plasma ADMA and Hcy related to the development of pre-eclampsia. RESULTS: Of the 252 women who completed the study, 179 had no complications, 49 developed pre-eclampsia, and 24 presented with complications other than pre-eclampsia. ADMA and Hcy increased gradually throughout pregnancy in the pre-eclampsia group, independent of maternal B-vitamin status and obesity, but remained constant in women with no complications. Relative to the preceding month, ADMA and Hcy levels increased 1 month prior to the onset of pre-eclampsia: 124 ± 27 nmol (P < 0.001) and 1177 ± 278 nmol (P = 0.001), respectively, in the pre-eclampsia group. The group of women with no complications did not show any significant changes. Increases of 80 nmol ADMA and 1000 nmol Hcy at 1 month prior to the onset of pre-eclampsia demonstrated the best potential for prediction. CONCLUSIONS: Increased ADMA and Hcy levels precede clinical manifestations of pre-eclampsia. Therefore, serial determinations of their concentrations may be helpful in identifying women at risk. TWEETABLE ABSTRACT: Increased ADMA and Hcy precede clinical pre-eclampsia and may identify women at risk.

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La enfermedad mineral ósea (EMO) es un término amplio que incluye a las alteraciones séricas del calcio, fósforo, vitamina D, paratohormona, anormalidades en el crecimiento, mineralización ósea y/o a las calcificaciones extraesqueléticas que acompañan al paciente con enfermedad renal crónica (ERC). Está presente en casi la totalidad de pacientes en diálisis y con el trasplante renal puede no siempre mejorar. Se han identificado nuevos factores y hormonas; como klotho y factor de crecimiento de fibroblastos-23 (FGF-23) que interactúan con la vitamina D y con la paratohormona en el manejo renal del calcio y fósforo. Ciertos reportes indican que son marcadores precoces del desarrollo de EMO, incluso cuando la función renal está levemente disminuida y los niveles de paratohormona son normales. La EMO ha sido asociada con mayor mortalidad, principalmente por su vinculación con la calcificación vascular. Este proceso conlleva a un incremento de eventos cardiovasculares que constituyen la principal causa de morbimortalidad en pacientes con ERC, sobre todo aquellos que se encuentran en diálisis, independientemente de la modalidad que los pacientes sigan. La forma de presentación de la EMO puede ser de alto o bajo recambio. Aunque no está completamente definido qué es lo que determina que se exprese una en particular, se ha encontrado que la enfermedad de bajo recambio se relaciona con malnutrición, uso inadecuado de calcitriol y diálisis ineficiente. El conocimiento de la EMO es relevante por su asociación con las complicaciones mencionadas y porque constituye un parámetro para evaluar la terapia instalada.

Mineral Bone Disorder (MBD) is a broad term that includes abnormal serum calcium, phosphorus, vitamin D, parathyroid hormone, growth abnormalities, bone mineralization and/or extraskeletal calcifications in patients with chronic kidney disease (CKD ). It is present in almost all patients on dialysis and may not always improve with a kidney transplant. New factors and hormones have been identified, such as Klotho and fibroblast growth factor-23 (FGF-23) that interact with vitamin D and the parathyroid hormone in the renal management of calcium and phosphorus. Some reports indicate that they are early markers of the development of MBD, even when kidney function is slightly decreased and parathyroid hormone levels are normal. MBD has been associated with higher mortality, mainly because of its link with vascular calcification. This process leads to an increase in cardiovascular events which are the leading cause of morbidity and mortality in CKD patients, especially those who are on dialysis, regardless of the modality that the patients follow. The presentation of the BMD can be of high or low turnover. Although it is not completely defined what determines that a particular form of presentation is expressed, it has been found that the low turnover disease is related to malnutrition, inappropriate use of calcitriol and inefficient dialysis. Knowledge of BMD is relevant for its association with the complications mentioned above and because it constitutes a parameter for assessing the instituted therapy.

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Epidemiological and experimental studies indicate that the altered fetal and neonatal environment influences physiological functions and may increase the risk of developing chronic diseases in adulthood. Because homocysteine (Hcy) metabolic imbalance is considered a risk factor for neurodegenerative diseases, we investigated whether maternal Vitamin B deficiency during early development alters the offspring's methionine-homocysteine metabolism in their brain. To this end, the dams were submitted to experimental diet one month before and during pregnancy or pregnancy/lactation. After birth, the offspring were organized into the following groups: control (CT), deficient diet during pregnancy and lactation (DPL) and deficient diet during pregnancy (DP). The mice were euthanized at various stages of development. Hcy, cysteine, glutathione (GSH), S-adenosylmethionine (SAM), S-adenosylhomocysteine (SAH), folate and cobalamin concentrations were measured in the plasma and/or brain. At postnatal day (PND) 0, total brain of female and male offspring exhibited decreased SAM/SAH ratios. Moreover, at PND 28, we observed decreased GSH/GSSG ratios in both females and males in the DPL group. Exposure to a Vitamin B-deficient diet during the ontogenic plasticity period had a negative impact on plasma folate and brain cortex SAM concentrations in aged DPL males. We also observed decreased plasma GSH concentrations in both DP and DPL males (PND 210). Additionally, this manipulation seemed to affect the female and male offspring differently. The decreased plasma GSH concentration may reflect redox changes in tissues and the decreased brain cortex SAM may be involved in changes of gene expression, which could contribute to neurodegenerative diseases over the long term.

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Helicobacter pylori es el agente causal de infección más frecuente de la especie humana, con una marcada desventaja entre los países desarrollados y los países en vía de desarrollo, donde es mucho más frecuente. Si bien la infección por Helicobacter pylori cursa asintomática en la mayoría de los individuos infectados también es claro que está íntimamente relacionada con enfermedades malignas del estómago como el cáncer gástrico y el linfoma MALT; y enfermedades benignas como la gastritis crónica y la úlcera péptica duodenal y gástrica. A partir del momento en que se conoció que la mucosa gástrica podía ser colonizada por una bacteria, en la literatura médica mundial indexada (PubMed) se han informado alrededor de una centena de manifestaciones extragástricas que involucran a especialidadesmédicas tan disímiles como la cardiología, la dermatología, la endocrinología, la ginecoobstetricia, la hematología, la neumología, la neurología, la odontología, la oftalmología, la otorrinolaringología, la pediatría, la siquiatría y vascular periférico, algunas de ellas con mayor o menor acervo probatorio de la relación entre la infección por Helicobacter pylori y el desarrollo de la enfermedad. Esta revisión de la literatura médica mundial se centra en el análisis de la relación de la infección por Helicobacter pylori con las deficiencias de hierro y de vitamina B12, con o sin anemia. Se presentan para ambas formas de anemia, una visión general del problema, las evidencias de la asociación de cada una de ellas con la infección por Helicobacter pylori, la fisiopatología y el manejo en la era poshelicobacter.

Helicobacter pylori is the most common causative agent of human infection, with a marked disadvantage between developed and developing countries. Although Helicobacter pylori infection is asymptomatic in majority of individuals infected, it is also clear their close relation with malignant diseases of the stomach as gastric cancer and gastric MALT lymphoma; and benign diseases such as chronic gastritis and duodenal and gastric peptic ulcer. Since the moment that was known that the gastric mucosa can be colonized by bacteria, it has been informed about a hundred extragastric events in the indexed world medical literature (PubMed), that involves medical specialties as diverse as cardiology,dermatology, endocrinology, obstetrics and gynecology, hematology, pulmonology, neurology, dentistry, ophthalmology, otolaryngology, pediatrics, psychiatry, and peripheral vascular. Some of these with varying proofs of relation between Helicobacter pylori infection and disease development. This review was focuses on the analysis of the relationship between Helicobacter pylori infection with the iron and vitamin B12 deficiencies, with or without anemia. The information is presented for both forms of anemia, the problem overview, evidence of the association with Helicobacter pylori infection, the pathophysiology and management in poshelicobacter era.

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