Introdução: Dispepsia funcional é uma doença que possui critérios diagnósticos definidos por reuniões de consenso, conhecidos por critérios de Roma. Apresenta alta prevalência mundial, grande impacto social e redução na qualidade de vida do indivíduo. Helicobacter pylori está envolvida na patogênese da dispepsia funcional, sendo indicada sua detecção e erradicação no tratamento dos pacientes dispépticos funcionais. H. pylori também tem sido sugerida como um importante agente na etiologia de níveis baixos de Vitamina B12 no soro. A hiperhomocisteinemia secundária à deficiência de Vitamina B12 e folato podem constituir um risco para as doenças cardiovasculares. Objetivo: investigar a relação entre os níveis séricos de Vitamina B12, folato e homocisteína e infecção pelo H. pylori em pacientes dispépticos funcionais. Métodos: Foram incluídos pacientes dispépticos funcionais, pelos critérios de Roma III do estudo HEROES (Helicobacter Eradication Relief of Dyspeptic Symptoms) - ClinicalTrials.gov número NCT00404534. Os pacientes dispépticos que apresentaram positividade para H. pylori foram randomizados para erradicação da bactéria com antibiticoterapia oral ou placebo. Após doze meses realizaram o segundo exame endoscópico com mesma metodologia. Da amostra total, 77 continuaram positivos para a infecação por H. pylori e 77 tiveram como resultado a erradicação da bactéria H. pylori, ou seja, negativaram. O material biológico foi previamente coletado e armazenado, além dos respectivos dados demográficos e clínicos. As amostras foram armazenadas a -80◦C em ependorf e realizadas medidas em soro dos níveis de vitamina B12 e folato e homocisteína. Resultados: Da amostra total, 77 pacientes eram H. pylori positivo (15 homens e 62 mulheres) e 77 eram H.pylori erradicados (21 homens e 56 mulheres). A média de idade foi de 47,8±11,5, em relação à idade e gênero não houve diferença significativa entre os grupos (p > 0,05). Quanto aos resultados reunidos em categorias (níveis de vitamina B12, folato e homocisteína), conforme os pontos de corte usados na literatura, não foi observada diferença estatisticamente significativa entre os dois grupos de pacientes (p > 0,6). Não houve correlação entre idade e níveis de vitamina B12 (p = 0,924). Houve diferença entre gêneros para homocisteína (p = 0,035), porém não houve significância para vitamina B12 (p = 0,584) e folato (p = 0,312). Não houve diferença entre níveis de homocisteína de pacientes H. pylori positivos e H. pylori erradicados para ambos os gêneros (p > 0,5). Conclusões: O presente estudo demonstrou que não houve relação significativa entre os níveis séricos de Vitamina B12, folato e homocisteína e infecção por H. pylori em relação aos H. pylori erradicados nos dispépticos funcionais. E quanto aos níveis de homocisteína comparados entre gêneros, os valores foram mais altos em homens. / Introduction: Functional dyspepsia a disease which has diagnosis criteria defined by consensus gatherings, known as the Rome criteria. It is highly prevalent worldwide, has great social impact, and reduces the quality of life of individuals. Helicobacter pylori is involved in the pathogenesis of functional dyspepsia, and its detection and eradication are indicated in the treatment of functional dyspepsia patients. H. pylori has also been suggested as an important agent in the etiology of low levels of vitamin B12 in serum. A hyperhomocysteinemia secondary to vitamin B12 and folate deficiencies could pose a risk for cardiovascular diseases. Objective: To investigate the relationship among the serum levels of Vitamin B12, folate and homocysteine, and the H. pylori infection in functional dyspeptic patients. Methodology: A group of patients with functional dyspepsia was included, following the Rome III criteria from the study HEROES (Helicobacter Eradication Relief of Dyspeptic Symptoms) – ClinicalTrials.gov number NCT00404534. The dyspeptic patients who were positive for H. pylori in tissue biopsy were randomized to eradication of the bacteria with oral antibiotic therapy or placebo. After twelve months, a second endoscopy was performed with the same methodology. Of the total sample, 77 patients remained positive for H. pylori and 77 patients had as a result the eradication of H. pylori bacteria, that is, they became negative. The biological material was previously collected and stored, besides its demographic and clinical data. The samples were stored at -80◦C in Eppendorf, they were measured in the serum of vitamin B12 folate and homocysteine levels. Results: Of the total sample, 77 patients were positive for H. pylori (15 men, 62 women) and 77 patients had the eradication of H. pylori (21 men, 56 women). The average age of the sample was about 47,8±11,5,regarding age and gender, it was not observed significant difference between the groups (p > 0,05). Concerning the results gathered into categories (the levels of vitamin B12, folate, and homocysteine), as the cut off points used in the literature, it was not observed statistically significant difference between the two groups of patients (p > 0,6). There was no correlation between age and vitamin B12 levels (p = 0,924). There was difference between genders for homocysteine (p = 0,035), but there was no significant difference for vitamin B12 (p = 0,584) and folate (p = 0,312). There was no difference between homocysteine levels of positive patients for H. pylori and H. pylori eradication in both genders (p > 0.5). Conclusions: The study showed no significant relationship between the serum levels of vitamin B12, folate, and homocysteine and the H. pylori infection in relation to H. pylori eradication in functional dyspeptic patients. Regarding homocysteine levels compared between genders, the values were higher in men.

Neural tube defects (NTDs), which is a congenital malformation, in significant part on the statistics of perinatal morbidity and mortality due to their high incidence rates. The DA can be limited to the central nervous system and / or peripheral, and may also include the overlying tissues (bones, muscles and connective tissue). Folic acid (FA) is a nutrient that plays a fundamental role in the process of cell multiplication. And the remarkable importance of folic acid in preventing NTDs where published studies portray the relationship between the levels of PA and the birth of children with NTDs, whereby the higher the rate of serum folate, less frequent are the births of children with NTDs . Although he knows that the AF is directly linked to the prevention of NTDs, little has been epidemiologically demonstrated the use of it in our population (especially from the Northeast-SE Brazil). All study women received prenatal (PN), however from the second month of conception outside the period in which it is contemplated by the AF prevention, highlighting the lack of an effective family planning. Was not performed by folic acid supplementation in 56.6% of women studied and the other 43.3% who did, began after the second month of pregnancy, which had become ineffective in the prevention, the same vitamin, the DTN. Showed that only 3.3% of cases of NTD group had a gestational age was less than 37 weeks and 50% were primigravida, the same group. The women studied were aged 24.8 years on average to become pregnant. Epidemiological parameters when compared with the comparison group, were similar, since both groups used the same health service, with the characteristic of high risk. The levels of serum folate in a group of women studied, remained normal and the highest of scientific studies published so far with similar characteristics. Prevention with the use of folic acid should be intensified by the various sectors of society, the risk group studied, so to avoid the recurrence of neural tube defects, reducing the incidence and recurrence in women who are more likely to generate conceptuses with this malformation. / O defeito do tubo neural (DTN), que é uma malformação congênita, participa de modo considerável nas estatísticas de morbidade e mortalidade perinatais devido a suas elevadas taxas de incidência. Os DTN, podem se limitar ao sistema nervoso central e/ou periférico, e também podem incluir os tecidos sobrejacentes (ossos, músculos e tecido conjuntivo). O ácido fólico (AF) é um micronutriente que apresenta papel fundamental no processo de multiplicação celular. E notória a importância do ácido fólico na prevenção dos DTN onde, estudos publicados retratam a relação dos níveis de AF e o nascimento de crianças com DTN, segundo os quais, quanto maior a taxa de folato sérico, menos frequentes são os nascimentos de crianças com DTN. Embora que saiba-se que o AF está ligado diretamente à prevenção do DTN, pouco se tem evidenciado epidemiologicamente o uso do mesmo na população brasileira (em especial a da região Nordeste/SE/Brasil). Todas as mulheres estudadas realizaram pré-natal (PN), entretanto a partir do segundo mês de concepção, fora do período que contempla-se a prevenção pelo AF, evidenciando a falta de um planejamento familiar efetivo. Não foi realizada a suplementação por ácido fólico em 56,6% das mulheres estudadas e as outras 43,3% que a fizeram, iniciaram após o segundo mês de gestação, o que tornara ineficaz a prevenção, pela mesma vitamina, ao DTN. Evidenciou-se que apenas 3,3% dos casos do grupo DTN tiveram idade gestacional foi inferior a 37 semanas e 50% foram primigesta, do mesmo grupo. As mulheres estudadas tiveram idade média ao engravidar 24,8 anos. Os parâmetros epidemiológicos, quando comparados com o grupo de comparação, mostraram-se semelhantes, uma vez que ambos os grupos utilizaram o mesmo serviço de saúde, com a característica de alto risco. Os níveis de ácido fólico sérico, em um grupo, das mulheres estudadas, mantiveram-se normais e mais elevados dos que os estudos científicos publicados até o momento com semelhantes características. A prevenção com o uso do ácido fólico deve ser intensificada pelos vários setores da sociedade, ao grupo de risco estudado, para evitarmos assim a recorrência do defeito do tubo neural, reduzindo a incidência e recorrência em mulheres que tem maior chance de gerarem conceptos com essa malformação.

O aborto espontâneo recorrente (AER) é definido pela ocorrência de três ou mais abortos espontâneos consecutivos com idade gestacional de até 20 semanas. O AER é um evento multifatorial, tem um índice de elucidação da causa na ordem de 50% e, mesmo com os avanços da medicina diagnóstica ainda assim 40% dos casos permanecem com sua causa desconhecida. O crescimento fetal é totalmente dependente do aporte de nutrientes oirundos da mãe, dentre esses nutrientes a cobalamina e o ácido fólico desempenham um papel fundamental para a viabilidade fetal. O objetivo geral deste estudo foi investigar se existe associação entre polimorfismos em genes relacionados ao metabolismo da cobalamina (MTHFR c.677C>T, TCN2 c. 776C>G e TCN2 c. 67A>G), e o aborto espontâneo recorrente. Os objetivos específicos deste estudo foram: 1 determinar se os polimorfismos MTHFR c. 677C>T, TCN2 c. 776C>G e TCN2 c. 67A>G estão associados ao aborto primário e secundário. 2 - Avaliar se os genótipos dos polimorfismos estudados estão relacionados com as concentrações séricas de cobalamina, folato e homocisteína total em mulheres com aborto espontâneo recorrente. Foram incluídas 256 mulheres com história de abortos espontâneos recorrentes, provenientes do Ambulatório de Obstetrícia da Clínica Obstétrica do Hospital das Clínicas da Faculdade de Medicina da USP e 264 mulheres saudáveis, sem história de aborto espontâneo e que tenham tido pelo menos duas gestações normais (grupo controle), pareadas segundo as idades. Foram colhidas amostras de sangue para a realização das dosagens bioquímicas, hormonais e das vitaminas e também para a realização das genotipagens dos polimorfismos por meio de PCR-RPFL (MTHFR c.677C>T , TCN c.776C>G e c. 67A>G). As dosagens bioquímicas e hormonais apresentaram resultados dentro dos limites de variação do normal. Quanto as concentrações de folato e cobalamina, houve diferença estatística significante entre os grupos p<0,05. As frequências dos genótipos e alelos para os polimorfismos estudados comparadas entre os grupos abortos primário, aborto secundário e grupo controle não apresentaram diferença estatística significante. Optamos a seguir por dividir o grupo de estudo entre abortos primários, onde não existe história de feto viável, e secundário neste caso onde há história de feto viável. Desta forma foram refeitas as análises estatísticas entre os grupos e encontramos diferença estatísticamente significante p<0,05 quando confrontamos os genótipos do polimorfismo TCN c.776C>G entre o grupo primário e o grupo controle. Em conclusão, quando comparamos as frequência dos genótipos e alelos em conjunto não apresentaram associação com o AER. Quando comparado separadamente o grupo de aborto primário e grupo controle houve diferença estatística significante associando o polimorfismo TCN2 c.776C>G ao AER primário. / The recurrent spontaneous abortion (RSA) is defined by the occurrence of three or more consecutive miscarriages with gestational age up to 20 weeks. The AER is a multifactorial event, has an index of elucidating the cause of around 50% and, even with advances in diagnostic medicine still remain 40% of cases with a known cause. Fetal growth is totally dependent on the supply of nutrients from the mother oirundos among these nutrients cobalamin and folic acid play a key role in fetal viability. The aim of this study was to investigate whether there is an association between polymorphisms in genes related to metabolism of cobalamin (MTHFR c.677C> T, c TCN2. 776c> G and c TCN2. 67A> G), and recurrent miscarriage. The specific objectives of this study were: 1 determine whether MTHFR c. 677C> T, TCN2 c. 776c> G and c TCN2. 67A> G are associated with abortion primary and secondary. 2 - Assess whether the genotypes studied polymorphisms are associated with serum concentrations of cobalamin, folate and total homocysteine in women with recurrent spontaneous abortion. We included 256 women with a history of recurrent miscarriages, from the Clinic of Gynecology, Obstetrics, Hospital das Clinicas, Faculty of Medicine, USP and 264 healthy women with no history of miscarriage and have had at least two normal pregnancies (group control), matched according to age. Blood samples were collected to perform the biochemical, hormonal and vitamins and also to perform the genotyping of polymorphisms by PCR-RPFL (MTHFR c.677C> T, TCN c.776C> G and c. 67A> G). The biochemical and hormonal results presented within the limits of normal variation. As the concentrations of folate and cobalamin, statistically significant difference between groups p <0.05. The frequencies of genotypes and alleles for the polymorphisms studied compared between groups abortions primary, secondary and abortion control group showed no statistically significant difference. We chose then to divide the study group between primary abortions where there is a history of viable fetus, and secondary in this case where there is a history of viable fetus. Thus were repeated statistical analyzes between groups and found statistically significant difference p <0.05 when confronted TCN genotypes of polymorphism c.776C> G between the primary group and the control group. In conclusion, when comparing the frequency of genotypes and alleles together apresntaram no association with AER. When compared separately the group of abortion primary and control group was statistically significant associated polymorphism TCN2 c.776C> G the primary AER.

Os consumos inadequados de cobalamina (Cbl) e de folato associados aos polimorfismos em genes de enzimas chaves do metabolismo da homocisteína podem agravar as comorbidades relacionadas a deficiências destas vitaminas. Os objetivos deste estudo foram avaliar o consumo de cobalamina, de folato e de vitamina 86 por gestantes através de três inquéritos recordatórios de 24 horas (IR24h); determinar as correlações entre as concentrações séricas de folato, de cobalamina, de metionina, de .S-adenosilmetionina (SAM), de Sadenosilhomocisteína (SAH), de homocisteína total (tHcy) e de ácido metilmalônico (MMA) com as vitaminas e as proteínas ingeridas na dieta pelas mulheres; analisar as associações entre os polimorfismos MTHFR C677T, MTHFR A1298C, MTR A2756G e MTRR A66G e alterações nas concentrações das vitaminas e dos metabólitos, além de avaliar os determinantes nutricionais e genéticos das concentrações dos metabólitos tHcy\" SAM, MMA e SAM/SAH durante a gestação. Participaram do estudo 73 mulheres com idades gestacionais de 16, 28 e 36 semanas, no qual foram aplicados três IR24h para cada gestante, um em cada idade gestacional. Foram realizadas as dosagens séricas de cobalamina sérica, folato sérico e eritrocitário, homocisteína total, metionina, MMA, SAM e SAH. As genotipagens dos polimorfismos MTHFR C677T, MTHFR A1298C, MTR A2756G e MTRR A66G foram feitas por PCR-RFLP. Observou-se que a ingestão de folato foi baixa em relação ao valor de 600 &#181;g/dia recomendado para gestantes, a ingestão de cobalamina foi menor que a encontrada na literatura, a ingestão de vitamina 86 e a de proteínas totais foram semelhantes às da literatura. As concentrações de Cbl séricas foram diretamente relacionadas com a ingestão de proteínas. As concentrações de MMA estavam relacionadas inversamente com a ingestão de cobalamina, com a ingestão das proteínas totais e com a renda per capita. Houve redução das concentrações de cobalamina sérica e aumento de MMA no decorrer das idades gestacionais, sendo observada maior concentração sérica de MMA entre as mulheres que ingeriram menos cobalamina. Não houve associação entre os polimorfismos MTHFR A1298C e MTRR A66G e as variações nas concentrações de vitaminas e de metabólitos. Com relação ao polimorfismo MTHFR C677T, as mulheres portadoras do alelo 677T possuíam menores concentrações médias de foiato eritrocitário, e para o polimorfismo MTR A2756G, as mulheres com genótipos AG e GG apresentaram menores concentrações de metionina. As concentrações aumentadas de tHcy foram explicadas pelas menores concentrações de folato eritrocitário, pela menor ingestão de proteínas totais, pelas maiores concentrações de creatinina sérica e pela ingestão de vitamina 86. A creatinina sérica foi a responsável pela variabilidade das concentrações da SAM. Maiores concentrações de folato sérico e menores concentrações de creatinina sérica foram os responsáveis pelo aumento dos valores da SAM/SAH. As maiores concentrações de MMA foram atribuídas à menor ingestão de cobalamina, à menor renda per capita e à menor concentração sérica de cobalamina. Conclusões: a ingestão de folato foi menor que a metade do recomendado. A ingestão de cobalamina atingiu o recomendado, no entanto não foi suficiente para manter o metabolismo materno. Os polimorfismos não foram associados a baixa ingestão de vitaminas para explicar as alterações nas concentrações de tHcy, da SAM, da SAM/SAH e do MMA. / The inadequate intake of cobalamin and folate associated to polymorphisms in key-enzyme genes of homocysteine can worsen comorbidities related to the deficiency of these vitamins. The aims of this study were to evaluate the intake of cobalamin, foiate and vitamin 86 by pregnant women through three 24-hour dietary recaIl (IR24h); to assess the correlation between serum concentrations of folate, cobalamin, methionine, S-adenosilmethionine (SAM), S-adenosilhomocysteine (SAH), total homocysteine (tHcy) and methylmalohic acid (MMA)towards vitamins and proteins intaked by women, to analyze association between MTHFR C677T, MTHFR A1298C, MTR A2756G and MTRR A66G polymorphisms and changes on vitamin and metabolites concentration, and to determine the nutritional and genetic determinants during a gestational period. 73 pregnant women participated in this study, with gestational ages of 16,28 and 36 weeks, onto whom were applied three IR24h to each woman, being one in each gestational age. Serum concentrations of cobalamin, foiate and red blood cell foiate, total homocysteine, methionine, MMA, SAM and SAH were evaluated. The polymorphisms of MTHFR C677T, MTHFR A1298C, MTR A2756G and MTRRA66G were performed by PCR-RFLP. It was observed that folate intake was low in relationship to recommended value for pregnant women of 600 &#181;g/day. Cobalamin intake was less than the one found in literature. Vitamin 86 and total protein intake was similar to the one found in literature. Serum Cbl concentrations were directly related to protein intake. MMA concentrations were in,verselycorrelated to cobalamin intake, to total proteins intakes and mounth per capita income. There were reduction of serum cobalamin concentration and enhance of MMAthroughout pregnancy weeks, being observed higher serum concentration of MMAamongst women that intaked less cobalamin. There was no association between MTHFRA1298Cand RRA66Gpolymorphism and the change in vitamins and metabolites concentrations. The women carrying allele 2756G for MTR polymorphism presented lesser serum methionine concentrations and alieie 677T for MTHFR C677T had less concentration of red blood cell folate. The red blood cell folate concentrations, intake of total proteins, serum creatinine concentrations and intake of vitamin 86 were eterminant of tHcy concentration. Serum creatinine was responsible for SAMconcentrations variability. Higher concentrations of serum foiate and lesse r concentrations of serum creatinine were responsible for the enhance of SAM/SAHvalues. The higher concentrations of MMAwere attributed to lesse r cobalamin intake, to lower per capita income and to lesser seruro concentration Df coba}amin. ConcJusions: lo/ate intake was less than ha(f of recommended amount, and cobalamina intake reached the recommended amount, however this amount was not enough to keeping the maternal metabolism. The poly~orphisms were not associated to low vitamin intake for explaining the changes Inserum concentrationsof tHcy,SAM,SAM/SAHand MMA.

O aborto espontâneo recorrente (AER) é caracterizado pela ocorrência de três ou mais abortos consecutivos e acomete 2-4% das mulheres em idade fértil. A etiologia está associada a vários fatores de risco, tais como anomalias uterinas, aberrações cromossômicas, autoimunidade, trombofilias, elevação na concentração de homocisteína (tHcy), porém cerca de 40% dos casos permanece sem causa definida. O metabolismo de unidades de carbono desempenha papel fundamental na disponibilidade de folato na célula, sendo essencial para o desenvolvimento placentário e fetal. Deficiência de vitaminas que regulam este metabolismo, como o ácido fólico, e polimorfismos em genes que codificam enzimas relacionadas ao metabolismo de folato (MTHFR, RFC1, GCP2 e MTHFD1) podem levar à redução das concentrações desta vitamina e ao aumento das concentrações de tHcy. Objetivo foi avaliar a associação entre polimorfismos em genes relacionados ao metabolismo do folato (RFC1, GCP2, MTHFR e MTHFD1) e o risco de se ter AER, bem como avaliar a associação entre estes polimorfismos e as alterações nas concetranções de folato, cobalamina e homocisteína. Foram constituídos três grupos: AER primário: 117 mulheres com AER e nenhum feto viável; AER secundário: 139 mulheres com AER e pelo menos um feto viável; e Controle: 264 mulheres sem história de aborto espontâneo. Nenhuma das mulheres estava grávida no momento da coleta do sangue. Amostras de sangue foram obtidas para dosagens bioquímicas (folato, Cbl, tHcy, entre outras), imunológicas e extração de DNA genômico. As genotipagens foram feitas por PCR-RFLP ou PCR em tempo real. As concentrações séricas de folato e Cbl foram maiores no AER primário e secundário (p<0,05). A distribuição dos genótipos de todos os polimorfismos foi semelhante nos três grupos. O aumento nas concentrações de folato sérico (OR: 1,05, 95% IC: 1,03 - 1,07, p<0,001), Cbl (OR: 1,00, 95% IC: 1,00 - 1,00, p= 0,016), tHcy (OR: 1,03, 95% IC: 0,97 - 1,11, p= 0,033) e T4 (OR: 1,02, 95% IC: 1,00 - 1,03, p= 0,006) e a presença de FAN reagente (1:160) (OR: 2,90, 95% IC: 1,25 - 6,75, p= 0,013) foram considerados fatores de risco para aborto primário. Para o aborto secundário, foram considerados fatores de risco o aumento nas concentrações de folato sérico (OR: 1,04, 95% IC: 1,02 - 1,05, p<0,001), Cbl (OR: 1,00, 95% IC: 1,00 - 1,00, p= 0,019) e tHcy (OR: 1,05, 95% IC: 1,00 - 1,09, p= 0,039), maiores idades (OR: 1,02, 95% IC: 0,98 - 1,06, p= 0,031), hábito de fumar (OR: 2,54, 95% IC: 1,41 - 4,60, p= 0,002) e ter maior IMC (OR:1,42, 95% IC: 1,07 - 1,88, p= 0,015). Os polimorfismos estudados não foram associados ao maior risco de se ter AER, quando analisados isoladamente, e também não foram associados a alterações nas concentrações séricas de folato, Cbl e tHcy, com exceção do genótipo MTHFR 677TT, cujas portadoras apresentaram maior concentração de tHcy, quando comparadas com as portadoras de genótipos 677CC e 677CT nos três grupos. As variáveis concentrações de folato, Cbl, tHcy e T4 e presença de FAN reagente foram associadas ao maior risco de se ter aborto primário. As variáveis idade, IMC, tabagismo, concentrações de folato, Cbl e tHcy foram associadas ao maior risco de aborto secundário. / The recurrent spontaneous abortion (RSA) is characterized by the occurrence of three or more consecutive miscarriages and affects 2-4% of women of childbearing age. The etiology is associated with several risk factors such as uterine abnormalities, chromosomal aberrations, autoimmunity, thrombophilia, increased concentration of homocysteine (tHcy). About 40% of cases remains unknown cause. The units of carbon metabolism plays an essential role in the availability of the cell folate, is essential for the placental and fetal development. A deficiency of the vitamins that regulate this metabolism, like folic acid, and polymorphisms in genes encoding enzymes related to folate metabolism (MTHFR, RFC1, and GCP2 MTHFD1) may lead to decreased concentrations of this vitamin and increased concentrations of tHcy. Objective was to evaluate the association between polymorphisms in genes related to folate metabolism (RFC1, GCP2, MTHFD1 and MTHFR) and the risk of having AER, and to evaluate the association between these polymorphisms and changes in concetranções folate, cobalamin, and homocysteine. Three groups were divided: AER primary: 117 women with RSA and no viable fetus, AER secondary: 139 women with RSA and at least one viable fetus and Control: 264 women with no history of miscarriage. None of the women was pregnant at time of blood collection. Blood samples were taken for biochemical (folate, Cbl, tHcy, etc.), immunological and genomic DNA extraction. The genotyping were carried out by PCR-RFLP or real time PCR. Serum concentrations of folate and Cbl were higher in groups 1 and 2 (p <0.05). The distribution of genotypes of MTHFR c.677C> T, MTHFR c.1298A> C, MTHFD1 c.1958G> A, RFC1 c.80G>GCP2 A and c.1561C> T was similar among the three groups. The increased concentrations of serum folate (OR: 1.05, 95% CI: 1.03 - 1.07, p <0.001), Cbl (OR: 1.00, 95% CI: 1.00 to 1.00, p = 0.016), tHcy (OR: 1.03, 95% CI: 0.97 to 1.11, p = 0.033) and T4 (OR: 1.02, 95% CI: 1.00 to 1.03, p = 0.006) and the presence of ANA (1:160) (OR: 2.90, 95% CI: 1.25 - 6.75, p = 0.013) were considered risk factors primary for abortion. For secondary abortion, were considered risk factors increased the concentrations of serum folate (OR: 1.04, 95% CI: 1.02 - 1.05, p <0.001), cobalamin (OR: 1.00, 95 % CI: 1.00 to 1.00, p = 0.019) and tHcy (OR: 1.05, 95% CI: 1.00 to 1.09, p = 0.039), higher age (OR: 1.02, 95% CI: 0.98 to 1.06, p = 0.031), cigarette smoking (OR: 2.54, 95% CI: 1.41 to 4.60, p = 0.002) and had a higher BMI (OR : 1,42,95% CI: 1.07 to 1.88, p = 0.015). The studied polymorphisms were not associated with increased risk of having RSA when analyzed separately, and were not associated with changes in serum folate, Cbl and tHcy, with the exception of the MTHFR 677TT genotype, whose patients had a higher concentration of total tHcy compared with those with 677CC and 677CT genotypes in the three groups. The variable concentrations of folate, Cbl, tHcy, and T4, presence of ANA and have been associated with increased risk for miscarriage primary. The variables age, BMI, smoking, concentrations of folate, Cbl and tHcy were associated with increased risk of secondary miscarriage.

Introdução: Frutas, legumes e verduras (FLV) contêm vários nutrientes com efeitos favoráveis para a saúde humana. Dentre estes, o folato é um dos nutrientes chaves envolvido na manutenção da saúde, com um potencial papel na redução das concentrações plasmáticas de homocisteína (hcy), reconhecido marcador de doença cardiovascular. Objetivos: Investigar o consumo de FLV, segundo características sóciodemográficas, antropométricas e de estilo de vida e relacionar o consumo de FLV e de folato com os níveis sanguíneos de hcy em adolescentes. Métodos: Este estudo utilizou dados de adolescentes de ambos os sexos, faixa etária de 12 a 19 anos, obtidos no Inquérito de Saúde ISA - Capital, realizado periodicamente no Município de São Paulo. O consumo de FLV foi estimado no estudo realizado em 2003, cuja amostra foi de 812 participantes. Para avaliação das relações entre FLV, folato e hcy, foram utilizados dados coletados no segundo ISA-Capital, entre os anos de 2008-2010 com amostra de 183 adolescentes. O consumo de FLV e de equivalentes de folato dietético (DFE), bem como o consumo de folato natural e ácido fólico, foram estimados por um recordatório de 24h. A análise bioquímica das concentrações plasmáticas de hcy foi realizada pelo método de cromatografia líquida. O ponto de corte de hcy plasmática utilizado foi de <8 mol/L para indivíduos com menos de 15 anos e <12 mol/L para indivíduos entre 15 e 19 anos. A concentração média de hcy plasmática foi descrita de acordo com os tercis de consumo de FLV, segundo as características sócio-demográficas, antropométricas e de estilo de vida. Todas as análises estatísticas foram realizadas no STATA® versão 10.0 considerando o nível de significância 5 por cento . Resultados: No primeiro estudo (2003) 20 por cento dos adolescentes não consumiram FLV no dia relatado e 6,5 por cento apresentaram consumo adequado. Renda, escolaridade do chefe da família e tabagismo influenciaram este consumo. Já no segundo estudo (2008-2010), 56 por cento não consumiram FLV e somente 4,9 por cento atingiram as recomendações. A prevalência de hiperhomocisteinemia na população estudada foi de 9,2 por cento . Adolescentes de 12 a 15 anos apresentaram menores valores de hcy (6,9mol/L) em comparação com os de 16 a 19 anos (8,4mol/L). Não foram encontradas diferenças significativas nos níveis plasmáticos de hcy analisados por tercis de consumo de FLV segundo características sócio-demográficas, de estilo de vida e antropométricas. Os alimentos que mais contribuíram com o consumo de DFE foram: pães (38,4 por cento ), seguidos pelo feijão (11,7 por cento ) e massas (10,1 por cento ). Para folato natural os alimentos de maior contribuição foram: feijão (30,3 por cento ), FLV (14,9 por cento ) e pães (14,6 por cento ); e, para o ácido fólico, se destacaram pães (53,3 por cento ), massas (14,6) e biscoitos (9,8 por cento ). Conclusão: O consumo de FLV por adolescentes está muito abaixo das recomendações nas duas amostras estudadas e não influenciou as concentrações plasmáticas de hcy / Background: Fruits and vegetables (FV) contains multiple nutrients with beneficial effects for human health. Among these, folate is one of the key nutrients involved in maintaining health, with a potential role in reducing plasma concentrations of homocysteine (hcy), recognized marker of cardiovascular disease. Objectives: To investigate the FV intake, according to socio-demographic, anthropometric and lifestyle characteristics and to relate the FV and folate intake with blood levels of hcy in adolescents. Methods: This study used data from adolescents of both sexes, aged 12 to 19, enrolled in the Health Survey ISA - Capital, periodically held in São Paulo. The FV intake was estimated in the study conducted in 2003, comprising 812 participants. To assess the relationship between FV, folate and hcy, we used data collected in the ISA Capital, conducted between the years 2008-2010 with a sample of 183 adolescents. The FV intake and dietary folate equivalents (DFE), as well as natural folate and folic acid intake, were estimated by a 24-hour recall. Biochemical analysis of plasma hcy was performed by liquid chromatography. The cutoff point for plasma hcy was <8 mmol/L for individuals younger than 15 years and <12 mmol/L for individuals aged between 15 and 19 years. The average concentration of plasma hcy was described into tertiles of FV intake, according to the socio-demographic, anthropometric and lifestyle characteristics. All statistical analyzes were performed in STATA ® version 10.0 with 5 per cent of significance level. Results: In the first study (2003) 20 per cent of adolescents not consumed FV on day evaluated and only 6.5 per cent had adequate intake. Per capita household income, head of familys level and smoking habit influenced this consumption. In the second study (2008-2010), 56 per cent not consumed FV and only 4.9 per cent met the recommendations. The prevalence of hyperhomocysteinemia was 9.2 per cent . Adolescents aged 12 to 15 years had lower levels of hcy (6.9 mmol/L) compared with 16 to 19 years (8.4 mmol/L). No significant differences were found in plasma levels of hcy into tertiles of FV intake according to socio-demographic, lifestyle and anthropometric characteristics. Foods that most contributed to DFE intake were bread (38.4 per cent ), followed by beans (11.7 per cent ) and pasta (10.1 per cent ). For natural folate, the foods that most contributed were: beans (30.3 per cent ), FV (14.9 per cent ) and breads (14.6 per cent ), and for folic acid, breads (53.3 per cent ), pasta (14.6) and biscuits (9.8 per cent ). Conclusion: FV intake by adolescents is below the recommendations and not influenced plasma concentrations of hcy

Bakgrund: Alzheimers sjukdom (AD) utgör vanligaste formen av demenssjukdomar i Sverige. Alzheimers sjukdom klassas som en neurodegenerativ sjukdom och karaktäriseras av proteininlagringar samt av hjärnatrofi. Ungefär 150 000 personer i Sverige lever idag med demenssjukdomar, varav 90 000 lider av AD och varje år insjuknar ytterligare 20 000 i demens. Vitamin B12 och folat anses utgöra en viktig del med avseende på hjärnans kognitiva funktioner. Låga nivåer av vitamin B12 och/eller folatbrist medför en höjning av Homocystein (Hcy) i blodet. Syfte: Syftet med examensarbetet var att undersöka det eventuella sambandet mellan nivåerna av vitamin B12, folat respektive Hcy och risken för att drabbas av Alzheimers sjukdom. Utifrån syftet ställdes 2 frågeställningar upp. Frågeställning 1: Finns det en risk att utveckla AD vid förändrade nivåer av folat, vitamin B12 och Hcy. Frågeställning 2: Finns det ett samband mellan förändrade nivåer av folat, vitamin B12 och Hcy vid diagnosticerad AD. Metod: Detta arbete är en litteraturstudie baserat på 7 vetenskapliga artiklar. Resultat: Samtliga fem studier utifrån frågeställning 2 visade att AD-patienter hade höga nivåer av Hcy än kontrollpatienterna. Två av dessa studier visade även att AD-patienterna hade lägre nivåer av både vitamin B12 och folat än kontrollindividerna. Två ytterligare studier av de fem samtliga visade också lägre nivåer av folat än kontrollgruppen.  Totalt 4 av 5 studier visade lägre nivåer av folat. Utifrån frågeställning 1 visade studie 1 att det var enbart de låga nivåerna av folat från baslinjen som förespråkade till insjuknande i AD. Studie 2 indikerade att individer med låga nivåer av vitamin B12 och folat har 2 gånger högre risk för att insjukna i AD. Slutsats: Det är fortfarande oklart idag huruvida nivåerna av vitamin B12, folat och Hcy påverkar riskerna för att utveckla AD. Studierna visar att det finns ett samband mellan markörerna kopplat till AD. Det krävs mer forskning för att fastställa det eventuella sambandet mellan vitamin B12, folat och Hcy. Fler patienter måste undersökas och flera studier bör utföras för att kunna fastställa associationerna av dessa ämnen med AD. Studierna visar att det finns ett samband mellan markörerna kopplat till AD. Fler studier som tar hänsyn till inklusionskriterierna med avseende på nutritionsstatus bör göras.  Detta eftersom lågt BMI (Body Mass Index) kan vara av betydelse för uppkomsten samt riskerna för att insjukna i AD. / Background: Alzheimer's disease (AD) is the most common form of dementia in Sweden. Alzheimer's disease is classified as a neurodegenerative disease and is characterized by protein deposits in certain parts of the brain accompanied with brain atrophy. 150 000 people in Sweden today suffer from dementia, of whom 90 000 suffer from AD and every year another 20 000 dementia cases reside. The highest risk factor of developing AD is old age. After the age of 65, the risk is considerably higher for developing AD. Vitamin B12 and folate is considered to be an important part with respect to the brain's cognitive functions. Folate acts as a donor of the methyl groups in a reaction catalysed by methionine synthase, which produce methyl cobalamin which needs to be metabolised to methionine from Homocystein (Hcy). Low levels of vitamin B12 and/or folate deficiency leads to an increase of Hcy in the blood. Objective: The aim of this study was to investigate the possible link between low levels of vitamin B12, folate and Hcy and the risk of developing Alzheimer's disease. Two question based on the objective of the study were set. Question 1: Is there any risk of developing AD with altered levels of folate, vitamin B12 and Hcy? Question 2: Is there a relationship between altered levels of folate, vitamin B12 and Hcy in diagnosed AD? Methods: This work is a literature study based on 7 scientific articles. Results: All five studies from question 2 showed that AD patients had high levels of Hcy compared to control patients. Two of these studies also revealed that AD patients had lower levels of both vitamin B12 and folate than control individuals. Furthermore 2 out of the 5 studies also displayed lower levels of folate compared to the control group, resulting in a total of 4 out of 5 studies showing lower levels of folate. Based on question 1, study 1 presented that only low levels of folate at baseline correlated with developing AD. Study 2 indicated that individuals with low levels of vitamin B12 and folate had twice times higher risk of developing AD. Conclusion: It is still unclear whether the levels of vitamin B12, folate and Hcy affect AD. The studies investigated show that there is a correlation between the investigated markers linked to AD. However, more research is needed to be able to determine the possible link between vitamin B12, folate and Hcy. More patients must be investigated and several studies should be performed to determine the associations of these subjects with AD.  More studies that take in consideration of nutritional status must be carried out, due to the fact that low BMI (Body Mass Index) may be of importance for the risk of developing AD.

One-carbon metabolism, a network of enzymatic reactions involving the transfer of methyl groups, depends on B-vitamins as cofactors, folate as a methyl group carrier, and amino acids, betaine, and choline as methyl group donors. One-carbon metabolism influences many processes in cancer initiation and development such as DNA synthesis, genome stability, and histone and epigenetic methylation. To study markers of one-carbon metabolism and inflammation in relation to colorectal cancer (CRC) risk, we used prediagnostic plasma samples from over 600 case participants and 1200 matched control participants in the population-based Northern Sweden Health and Disease Study cohort. This thesis studies CRC risk with respect to the following metabolites measured in pre-diagnostic plasma samples: 1) folate, vitamin B12, and homocysteine; 2) components of one-carbon metabolism (choline, betaine, dimethylglycine, sarcosine, and methionine); and 3) three markers of different aspects of vitamin B6 status. In addition, this thesis examines three homocysteine ratios as determinants of total B-vitamin status and their relation to CRC risk. In two previous studies, we observed an association between low plasma concentrations of folate and a lower CRC risk, but we found no significant association between plasma concentrations of homocysteine and vitamin B12 with CRC risk. We have replicated these results in a study with a larger sample size and found that low folate can inhibit the growth of established pre-cancerous lesions. Using the full study cohort of over 1800 participants, we found inverse associations between plasma concentrations of the methionine cycle metabolites betaine and methionine and CRC risk. This risk was especially low for participants with the combination of low folate and high methionine versus the combination of low folate and low methionine. Well-functioning methionine cycle lowers risk, while impaired DNA synthesis partly explains the previous results for folate. We used the full study cohort to study associations between CRC risk and the most common marker of vitamin B6 status, pyridoxal' 5-phosphate (PLP), and two metabolite ratios, PAr (4-pyridoxic acid/(PLP + pyridoxal)) estimating vitamin B6 related inflammatory processes and the functional vitamin B6 marker 3-hydroxykynurenine to xanthurenic acid (HK:XA). Increased vitamin B6-related inflammation and vitamin B6 deficiency increase CRC risk. Inflammation was not observed to initiate tumorigenesis. Total B-vitamin status can be estimated by three different recently introduced homocysteine ratios. We used the full study cohort to relate the ratios as determinants of the total B-vitamin score in case and control participants and estimated the CRC risk for each marker. Sufficient B-vitamin status as estimated with homocysteine ratios was associated with a lower CRC risk. These studies provide a deeper biochemical knowledge of the complexities inherent in the relationship between one-carbon metabolism and colorectal tumorigenesis.

We used the GENECONV program, the Hsu et al. (2010) method and phylogenetic analyses to analyze the gene conversions which occurred in the growth hormone, folate receptor and trypsin gene families of six primate species. Significant positive correlations were found between sequence similarity and conversion length in all but the trypsin gene family. Converted regions, when compared to non-converted ones, also displayed a significantly higher GC-content in the growth hormone and folate receptor gene families. Finally, all detected gene conversions were found to be less frequent in conserved gene regions and towards functionally important genes. This suggests that purifying selection is eliminating all gene conversions having a negative functional impact.

Dementia is prevalent among elderly people. As the world population ages, it is projected that the number of people affected by dementia may triple in the next 50 years. Over the last two decades, research has focused on identifying potentially modifiable risk factors in development and progression of dementia, such as vitamin B12 and folate. Results concerning the effects of low folate and vitamin B12 on cognitive performance are mixed. The main objective of the present study was to investigate the effects of vitamin deficiency on cognitive functioning in a clinical sample of elderly individuals with cognitive problems using a comprehensive neuropsychological assessment. A retrospective chart-review was performed on the 102 records of patients from the Geriatrics Clinic at the University of North Texas Health Science Center who presented with cognitive deficits. Charts were reviewed to obtain data on vitamin supplementation, vitamin status, history of chronic conditions and other biochemical data. The available database was used to obtain data on neuropsychological assessment. The study demonstrated mild association between vitamin B12 and folate status and cognitive deficits. There appeared to be a higher cut-off level that is above the traditionally used levels for vitamin B12 and folate deficiency concentrations at which cognitive deficits became more pronounced. Clinical applications, limitations and suggestions for future research were discussed.