RESUMO
Interest in nonpharmaceutical supplements for treating major depressive disorder (MDD) has increased signiï¬cantly, both among patients and among clinicians during the past decades. Despite the large array of antidepressants (ADs) available, many patients continue to experience relatively modest response and remission rates, in addition to a burden of side effects that can hinder treatment compliance and acceptability. In this article, we review the literature on folates and S-adenosylmethionine (SAMe), 2 natural compounds linked in the 1-carbon cycle metabolic pathway, for which substantial evidence supports their involvement in mood disorders. Background information, efï¬cacy data, proposed mechanisms of action, and side effects are reviewed. Based on existing data, supplementation with SAMe, as well as with various formulations of folates, appears to be efficacious and well tolerated in reducing depressive symptoms. Compared with other forms of folates, 5-methyltetrahydrofolate (L-methylfolate or 5-MTHF) may represent a preferable treatment option for MDD given its greater bioavailability in patients with a genetic polymorphism, and the lower risk of specific side effects associated with folic acid. Although further randomized controlled trials in this area appear warranted, SAMe and L-methylfolate may represent a useful addition to the AD armamentarium.
Assuntos
Transtorno Depressivo Maior/tratamento farmacológico , Ácidos Pteroilpoliglutâmicos/uso terapêutico , S-Adenosilmetionina/uso terapêutico , Adulto , Antidepressivos/efeitos adversos , Antidepressivos/uso terapêutico , Transtorno Depressivo Maior/fisiopatologia , Transtorno Depressivo Maior/psicologia , Transtorno Depressivo Resistente a Tratamento/tratamento farmacológico , Transtorno Depressivo Resistente a Tratamento/fisiopatologia , Transtorno Depressivo Resistente a Tratamento/psicologia , Método Duplo-Cego , Quimioterapia Combinada , Medicina Baseada em Evidências , Humanos , Transferases de Grupo de Um Carbono/fisiologia , Ácidos Pteroilpoliglutâmicos/efeitos adversos , Ácidos Pteroilpoliglutâmicos/fisiologia , Ensaios Clínicos Controlados Aleatórios como Assunto , S-Adenosilmetionina/efeitos adversos , S-Adenosilmetionina/fisiologia , Tetra-Hidrofolatos/efeitos adversos , Tetra-Hidrofolatos/fisiologia , Tetra-Hidrofolatos/uso terapêuticoRESUMO
Homocysteine metabolism is influenced by genetic polymorphisms of the methylenetetrahydrofolate reductase (MTHFR 677 C-->T and 1298 A-->C) and transcobalamin genes (TCN1 776 C-->G ). We evaluated the association of homocysteine with Alzheimer's disease (AD) and the influence of related polymorphisms and APOE, in 180 cases and 181 controls from southern Italy. Homocysteine (upper tercile) was associated with AD risk, with an odds ratio of 2.8 (95% confidence interval (CI) 1.54-5.22, p=0.0008), which was increased 2.2- and 2.0-fold by MTHFR 677T (odds ratio 6.28, 95% CI 2.88-16.20, p < 0.0001) and APOE epsilon4 (odds ratio: 5.60, 95% CI 1.12-28.05, p=0.0361), respectively. In conclusion, association of homocysteine with AD was aggravated by MTHFR 677T and APOE epsilon4 alleles.
Assuntos
Doença de Alzheimer/sangue , Homocisteína/sangue , Metilenotetra-Hidrofolato Redutase (NADPH2)/genética , Polimorfismo Genético , Fatores Etários , Idoso , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/genética , Apolipoproteína E4 , Apolipoproteínas E/genética , Apolipoproteínas E/metabolismo , Estudos de Casos e Controles , Intervalos de Confiança , Feminino , Humanos , Masculino , Metilenotetra-Hidrofolato Redutase (NADPH2)/metabolismo , Pessoa de Meia-Idade , Análise Multivariada , Razão de Chances , Ácidos Pteroilpoliglutâmicos/uso terapêutico , Análise de Regressão , Estatísticas não Paramétricas , Transcobalaminas/genética , Transcobalaminas/metabolismo , Vitamina B 12/uso terapêuticoAssuntos
Doença das Coronárias/sangue , Homocisteína/sangue , Biomarcadores/sangue , Doença das Coronárias/etiologia , Doença das Coronárias/prevenção & controle , Humanos , Hiper-Homocisteinemia/sangue , Hiper-Homocisteinemia/complicações , Hiper-Homocisteinemia/tratamento farmacológico , Ácidos Pteroilpoliglutâmicos/uso terapêutico , Fatores de Risco , Índice de Gravidade de DoençaRESUMO
A new anti-folate, 7-hydro-8-methylpteroylglutamylglutamic acid, was isolated from the culture broth of a soil actinomycete. The antibiotic inhibited the growth of Enterococcus faecium which requires folic acid. The inhibitory action was reversed by thymidine or excess amounts of folate-related compounds such as pteroic acid, folic acid, dihydrofolic acid and leucovorin. It inhibited thymidylate synthase from E. faecium, Bacillus subtilis and Ehrlich ascites carcinoma cells.