O Supremo Tribunal Federal relativizou a Constituição

O Supremo Tribunal Federal relativizou a Constituição

 

09 março, 2012

 

Sérgio Abranches

 

O Supremo Tribunal Federal voltou atrás na decisão que considerava inconstitucional a medida provisória que criou o ICMBIO. Pelo menos 560 outras MPs padeciam da mesma grave falha legal: não haviam passado por uma Comissão Mista do Congresso, como manda a Constituição. Por isso, o STF decidiu relativizar a Constituição.

 

O Advogado Geral da União levantou questão de ordem sobre a decisão que considerou procedente a Ação de Inconstitucionalidade da lei que criou o Instituto Chico Mendes, argumentando que a decisão do STF na prática corresponderia a considerar inconstitucionais todas as MPs que haviam desobedecido à Constituição. Seriam “centenas” segundo ele. Matéria de Carolina Brígido para O Globo, diz que são 560 medidas provisórias que seriam consideradas inconstitucionais. Passando o pente fino podem ser até mais. A ministra Carmen Lúcia lembrou, por exemplo, durante o julgamento que tomou a decisão juridicamente correta, dos “contrabandos” recorrentes: matérias estranhas ao objeto da medida provisória, inseridas à sorrelfa e ilegalmente. A ministra não disse porque esse hábito. É porque essas matérias, isoladamente, não seriam aprovadas ou causariam justificada contestação. Há estudos de juristas e politólogos mostrando que a maioria absoluta das MPs não poderia ter passado da Comissão de Constituição e Justiça, por não atenderem aos preceitos constitucionais para esse instrumento que deveria ser excepcional e se tornou a regra.

 

Diante do argumento sobre o transtorno de rever tantas medidas provisórias, os ministros decidiram que só a partir de ontem, 5a feira, dia 8 de março de 2012, a regra constitucional deverá ser obedecida. Prevaleceu o fato consumado, por pragmatismo, em nome de suposta “segurança jurídica”. A obediência à Constituição se tornou relativa e com data marcada. Uma coisa é marcar data e vigência de lei para obedecer aos princípios da não retroatividade e da anualidade, por exemplo. Outra é considerar legal o ilegal por conveniência e marcar encontro futuro entre os Poderes da República e a constitucionalidade.

 

Comentei na CBN, ontem, que a MP da reforma que criou o ICMBIO era substantivamente ruim. O STF aduziu que era inconstitucional. Portanto nasceu sem a necessária qualidade técnica e administrativa e foi aprovada com grave vício de procedimento legislativo, que feriu o princípio constitucional.

 

Substantivamente, ela deixou em pior condição o IBAMA, de cuja costela saiu o ICMBIO, para cuidar das unidades de conservação. Este, nasceu anêmico e continua cronicamente fraco e sem recursos suficientes para cumprir suas funções. O IBAMA acabou desmoralizado em várias ocasiões. Suas decisões técnicas foram muitas vezes atropeladas por pragmáticas decisões políticas. O caso mais escandaloso é o das licenças para a hidrelétrica de Belo Monte. Como o STF havia autorizado a continuidade do funcionamento do ICMBIO e dado ao Congresso dois anos de prazo para fazer uma lei de acordo com as normas constitucionais, não haveria descontinuidade administrativa. Mas o Executivo e o Legislativo teriam que obedecer à Constituição, o que parece óbvio, mas no Brasil não é. Argumentei que seria a oportunidade para a ministra Izabella Teixeira apresentar à presidente Dilma Rousseff uma boa proposta de reforma do Meio Ambiente, dando condições mais apropriadas ao IBAMA e ao ICMBIO e mais musculatura e centralidade ao próprio ministério. O comentário está aqui.

 

Quinta, 08/03/2012

“Uma boa oportunidade para uma reforma efetiva do Ministério do Meio Ambiente”

 

 

O recuo do STF, um “jeitinho”, que já havia sido denunciado pelo ministro Joaquim Barbosa em outra ocasião de revisão de decisão já tomada, transcende a questão do ICMBIO e do Meio Ambiente. A decisão relativiza a obediência à Constituição, reforçando a cultura brasileira de leis que pegam e não pegam, enfraquece o primado da lei no país. É tipicamente um caso de desmoralização institucional. Para não causar transtorno, o que é ilegal passa a ser legal, por um tempo, mas tem que ser legal daí em diante. É kafkiano, sem a criatividade do mestre do absurdo.

 

Esses despropósitos vão emaranhando o Brasil em uma teia de transgressões consentidas, de leis validadas pela metade, de fatos consumados que se sobrepõem ao primado da lei. No caso, ao primado da Constituição. E os agentes dessa coalizão pela relativização do respeito à Constituição são o Advogado Geral da União e os ministros do Supremo Tribunal Federal. Os transgressores originais da Constituição são os Poderes Legislativo, que descumpriu procedimentos constitucionais, e Executivo que promulgou lei inconstitucional.

 

É grave. Para o STF não poderia haver forma de ajeitar as coisas diante de uma inconstitucionalidade flagrante. Ou o ato é inconstitucional, ou não é; ou é ilegal, ou não é. É chocante ver a Corte Suprema dizer que uma lei é inconstitucional, mas tudo bem desobedecer à Carta Magna, porque muitas leis são igualmente inconstitucionais, e que só daqui para a frente nova desobediência não será tolerada. É como aqueles pais tolerantes, diante do filho reincidente, que dizem: “desta vez, passa, mas daqui para a frente não vamos mais tolerar esse comportamento”. E toleram, porque o reincidente, reincidirá.

 

É essa cultura do “desta vez passa”, da multa que não é cobrada, da pena que não é cumprida, que permite que caçadores, desmatadores, palmiteiros, mineradores, invadam as unidades de conservação e depredem seu patrimônio natural, destruam sua biodiversidade. O ICMBIO sem meios, pouco pode fazer. É essa relatividade da lei que alimenta os desmatadores que estão devastando a Amazônia, o Cerrado e atacam o que resta de Mata Atlântica. É o fato consumado que permite obras em desrespeito evidente da legislação ambiental e da própria Constituição sejam licenciadas. É a lei que não pega que permite que a corrupção se alastre, o crime compense, a governança se enfraqueça.

 

A desmoralização decorrente das instituições não ameaça apenas o meio ambiente, o patrimônio púbico e a segurança coletiva. Põe em risco o próprio estado de direito. As leis são substituídas pelas urgências pragmáticas e pela conveniência. Não é boa jurisprudência.

 

Meu novo comentário na CBN está aqui.

 

Economia marrom ganha espaço no penúltimo dia da Rio+20

“Durante discurso, Evo Morales comentou sobre a expansão da exploração de petróleo na Bolívia. Já Guido Mantega falou sobre a importância da economia do combustível fóssil no Brasil.”

 

Fonte

http://www.ecopolitica.com.br/2012/03/09/o-supremo-tribunal-federal-relativizou-a-constituicao/

A importância do consumo dietético de cálcio e vitamina D no crescimento

Crescimento das crianças

A importância do consumo dietético de cálcio e vitamina D no crescimento

Jornal de PediatriaJornal de Pediatria

Print version ISSN 0021-7557

fonte

http://www.scielo.br/scielo.php?pid=S0021-75572008000600003&script=sci_arttext

 

J. Pediatr. (Rio J.) vol.84 no.5 Porto Alegre Sept./Oct. 2008

http://dx.doi.org/10.2223/JPED.1816

 

ARTIGO DE REVISÃO

 

A importância do consumo dietético de cálcio e vitamina D no crescimento

 

 

Aline L. BuenoI; Mauro A. CzepielewskiII

 

INutricionista. Mestre, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, RS
IIMédico. Doutor, Universidade Federal de São Paulo – Escola Paulista de Medicina (UNIFESP-EPM), São Paulo, SP. Professor associado, Programa de Pós-Graduação em Ciências Médicas: Endocrinologia e Nutrição, Faculdade de Medicina, UFRGS, Porto Alegre, RS

Correspondência


 

RESUMO


OBJETIVO:
Verificar o papel nutricional do cálcio e da vitamina D no processo de crescimento e desenvolvimento infanto-juvenil, visando, em especial, a prevenção e o tratamento do atraso de crescimento causado por deficiência nutricional.

 

FONTES DOS DADOS: As informações foram coletadas a partir de artigos publicados nas 2 últimas décadas, pesquisados nas bases de dados SciELO, PubMed e MEDLINE, livros técnicos e publicações de organizações internacionais.
SÍNTESE DOS DADOS: O crescimento sofre influência de fatores intrínsecos (genéticos e metabólicos) e extrínsecos (fatores ambientais, como alimentação, saúde, higiene, habitação, e o acesso aos serviços de saúde). Entre os fatores nutricionais, destacam-se as deficiências de vitaminas e oligoelementos que podem se associar à desnutrição ou depender da absorção insuficiente dos mesmos. Sendo o cálcio um dos principais componentes do tecido mineral ósseo, este é essencial para uma adequada formação óssea e, considerando que a vitamina D desempenha papel importante no metabolismo do cálcio, uma dieta insuficiente nesses nutrientes pode influenciar a formação do esqueleto e o processo de crescimento e desenvolvimento.

 

CONCLUSÕES: A baixa ingestão ou baixa absorção de cálcio e vitamina D em crianças e adolescentes pode limitar seu desenvolvimento estatural, sendo necessário fornecer quantidades suficientes de ambos na fase crítica do crescimento.

 

Palavras-chave: Transtornos do crescimento, raquitismo, ingestão de alimentos, recomendações nutricionais.


 

 

Introdução

 

O crescimento somático normal é um processo complexo determinado por fatores celulares, interação genética e também por fatores externos, como atividade física, infecções, aspectos psicossociais e econômicos, doenças crônicas, fatores metabólicos e hormonais e, finalmente, alimentação1. De modo geral, todo indivíduo nasce com um potencial genético de crescimento, que poderá ou não ser atingido, dependendo das condições de vida a que esteja submetido. Assim, pode-se dizer que a altura final é o resultado da interação entre sua carga genética e os fatores do meio ambiente que permitirão a maior ou menor expressão do seu potencial genético2,3.

 

O crescimento deficiente pode manifestar-se clinicamente como estatura abaixo do esperado para o potencial familiar, estatura abaixo do esperado para a população geral ou por velocidade de crescimento inferior à esperada, considerando o sexo, a idade cronológica e o estágio puberal da criança. Portanto, a criança com baixa estatura, por definição, é aquela que se encontra abaixo do percentil 3, ou seja, 2 desvios padrão nos gráficos de crescimento para a média de estatura da população geral4,5.
Então, como o crescimento normal depende da interação entre vários fatores, a baixa estatura pode ser resultante de diversas causas, entre elas as causas genéticas, endócrinas, secundárias a doenças crônicas e as causas nutricionais.

 

Infecções e consumo alimentar inadequado estão bem estabelecidos como causas de baixa estatura6,7. Contudo, a possibilidade da deficiência de algum micronutriente ter algum papel na etiologia do retardo de crescimento tem despertado atenção recentemente. Isso porque alguns micronutrientes são requisitos para promoção do crescimento físico, para a maturação sexual, para o desenvolvimento neuromotor e para a integridade e o funcionamento do sistema imune. Assim, o completo potencial genético de uma criança para o crescimento físico e desenvolvimento mental pode também ser comprometido devido a deficiências subclínicas de micronutrientes8.

 

Como causa dietética de baixa estatura caracterizada pela deficiência de um micronutriente, destacamos o raquitismo causado pela deficiência de vitamina D, doença que resulta em retardo de crescimento, fraqueza muscular, deformidade esquelética, hipocalcemia e tetania. Epidemia no século XIX foi quase completamente erradicada com o encorajamento da exposição solar e com a fortificação do leite em vitamina D. Mas a deficiência desta vitamina voltou a ser uma epidemia entre crianças, e o raquitismo tornou-se assunto de saúde em todo o mundo. Além da deficiência de vitamina D, a deficiência de cálcio causa raquitismo9.

 

Contudo, acreditamos que, mesmo antes do desenvolvimento do raquitismo, a deficiência dietética de cálcio e vitamina D pode prejudicar o crescimento e desenvolvimento. Assim, esta revisão sumariza o papel do cálcio e da vitamina D e sua importância na manutenção da saúde geral, crescimento e desenvolvimento de crianças e adolescentes.

 

Cálcio

 

O cálcio é um elemento fundamental ao organismo, e sua importância está relacionada às funções que desempenha na mineralização óssea, principalmente na saúde óssea, desde a formação, manutenção da estrutura e rigidez do esqueleto10,11.

 

O cálcio absorvido da dieta depende do balanço entre a ingestão, a absorção (ingestão menos a perda fecal) e a excreção. Vários fatores influenciam estes mecanismos, conforme apresentado na Tabela 111,12.

 

 

Recomendações nutricionais de cálcio

 

As recomendações nutricionais de cálcio variam durante a vida dos indivíduos, com maiores necessidades durante períodos de rápido crescimento, como na infância e na adolescência, durante a gravidez e lactação, na deficiência de cálcio, na prática de exercícios que resultem em alta densidade óssea e aumentam a absorção de cálcio e na velhice13. A ingestão ideal de cálcio é aquela que conduza a um pico de massa óssea adequado na criança e adolescente, mantenha-o no adulto e minimize a perda na senilidade14.

 

O Standing Commitee on the Scientific Evaluation of Dietary Reference Intakes, o Food and Nutrition Boarde o Institute of Medicine – National Academy Science estabeleceram recomendações dietéticas para cálcio em vários grupos etários. Os requerimentos de cálcio foram estabelecidos baseados em três indicadores: risco de fratura, medidores de massa muscular e retenção máxima de cálcio12,15 (Tabela 2).

 

 

 

 

Todavia, apesar do acordo entre os países desenvolvidos quanto às recomendações dietéticas de cálcio, existem algumas dúvidas quanto à sua aplicação em países em desenvolvimento, como o Brasil, pois todas as tabelas são baseadas em dados sobre população branca de países desenvolvidos, desconsiderando as diferenças de etnia, hábitos culturais e alimentares e geográficas observadas nos países10. Salientamos, assim, a necessidade de desenvolver recomendações dietéticas específicas para nossa população, considerando as variações regionais tão diversas do nosso país.

 

Por não ser produzido endogenamente, o cálcio é somente adquirido através da ingestão diária de alimentos que o contenham14. Como alimentos ricos em cálcio, destacam-se o leite e seus derivados (iogurte e queijo) com baixo teor de gorduras16.

 

A alta biodisponibilidade do cálcio nos produtos lácteos está relacionada com o conteúdo de vitamina D e com a presença de lactose, que aumentam a sua absorção no intestino17. Além disso, como o pH do leite é alcalino, o cálcio se mantém em suspensão pela formação de caseinato de cálcio, de citrato de cálcio e de um complexo com a lactose. Assim, a lactose, caseinato e citrato presentes no leite e derivados parecem explicar a melhor absorção de cálcio destas fontes em relação a outras14. Apesar dos queijos conterem pouca lactose, o cálcio está prontamente disponível neste alimento10.

 

Recentemente, com o diagnóstico mais freqüente de intolerância a lactose, esta situação exige cuidado especial na manutenção da ingestão adequada de cálcio nestes pacientes. Esta hipótese é reforçada pelos resultados de Medeiros17, que encontraram menor ingestão de cálcio (p < 0,001) entre crianças que consumiam dieta isenta de leite de vaca e derivados18.

 

Entretanto, não somente o consumo de leite e derivados contribui para a ingestão de cálcio dos indivíduos. São fontes de cálcio vegetais de folhas verdes escuras, tais como couve, couve-manteiga, folhas de mostarda, de brócolis e de nabo, mas o cálcio está pouco biodisponível nesses alimentos. Sardinha, moluscos bivalves, ostras, salmão e leguminosas, como a soja, também contêm cálcio em quantidades descritas na Tabela 310,19,20.

 

 

 

 

Consumo dietético de cálcio

 

Até recentemente, não se acreditava que o baixo consumo de cálcio resultasse em prejuízos à saúde. Atualmente se considera que variações mundiais na prevalência da deficiência de cálcio podem influenciar a distribuição óssea e os hábitos alimentares nas diferentes populações, em decorrência de diferenças genéticas, étnicas, geográficas (latitudes), e relacionadas a fatores culturais e estilo de vida11.

 

Podemos citar alguns estudos que demonstram baixo consumo de alimentos que contenham cálcio, especialmente em idade de desenvolvimento físico, fato que pode futuramente causar déficit de crescimento ou até doenças ósseas.

 

Rajeshwari et al. acompanharam crianças dos 10 anos até a vida adulta, demonstrando que o consumo de cálcio está diminuído durante este período, apesar do aumento do consumo energético. Além disso, verificou que há diminuição considerável no consumo total de cálcio na infância (54% abaixo da recomendação) à idade adulta (77% abaixo da recomendação)21.

 

Em outro estudo, Salamoun et al. avaliaram o consumo de cálcio e vitamina D entre crianças e adolescentes de países do mediterrâneo e encontraram consumo subótimo de ambos os nutrientes (consumo médio de cálcio de 816±776,8 mg/dia e de vitamina D de 129±116,1 UI/dia). Apenas 12% atingiram o consumo diário adequado de cálcio, e 16% de vitamina D22.

 

No Brasil, Lerner et al. avaliaram o consumo de cálcio em adolescentes de escolas públicas de Osasco (SP) e encontraram que o consumo médio diário de cálcio não foi significativamente diferente entre meninos e meninas, estando, nos dois casos, perto de 50% do recomendado (média de ingestão de cálcio de 628,85±353,82 mg/dia entre os meninos e 565,68±295,43 mg/dia entre as meninas). Somente 6,2% dos meninos e 2,8% das meninas apresentaram consumo adequado em cálcio, à semelhança de outros estudos realizados no exterior21-23.

 

 

Vitamina D

 

A 1,25-(OH)2D3 é um hormônio que regula o metabolismo do cálcio e do fósforo. Assim sendo, sua principal função é manter os níveis séricos de cálcio e fósforo em um estado normal capaz de propiciar condições à maioria das funções metabólicas, entre elas a mineralização óssea9,16. Por estar envolvida no crescimento esquelético, a vitamina D torna-se essencial durante a infância e a adolescência24.

 

Níveis séricos normais de vitamina D promovem a absorção de 30% do cálcio dietético e mais de 60-80% em períodos de crescimento, devido à alta demanda de cálcio25. Por isso, durante a infância, a deficiência de vitamina D pode causar retardo de crescimento, anormalidades ósseas, aumentando o risco de fraturas na vida adulta26.

 

Recomendações nutricionais de vitamina D

 

As recomendações nutricionais diárias de vitamina D são difíceis de estabelecer com exatidão, pois ela é produzida endogenamente e depositada no tecido adiposo por longos períodos de tempo, e suas necessidades também dependem do consumo dietético de cálcio e fósforo, idade, sexo, pigmentação da pele e exposição solar. Historicamente se definiu como quantidade de vitamina D suficiente para prevenir o raquitismo uma colher de sopa de óleo de peixe. Ainda hoje não existem evidências suficientes para estabelecer sua recomendação, mas seu consumo adequado diário foi estabelecido26,27,15 (Tabela 4).

 

 

A pele tem alta capacidade de sintetizar vitamina D, pois a exposição solar que causa leve eritema na pele em crianças e adultos vestindo trajes de banho é estimada como sendo igual a 15 vezes a recomendação diária de vitamina D, e a exposição a um eritema leve em 6% do corpo é igual a um consumo de 15-25 µg de colecalciferol26,28.

 

Ainda assim é difícil determinar a quantidade de exposição solar (superfície total de pele exposta em um determinado tempo) necessária para prevenir a deficiência de vitamina D e o raquitismo na infância. Além disso, há uma preocupação crescente quanto à exposição UVB nesta fase e sua relação com o câncer de pele na vida adulta, pois existe uma correlação positiva entre a ocorrência de melanoma maligno entre adultos e a quantidade de exposição solar na infância29.

 

Apesar de a vitamina D ser produzida por exposição da pele aos raios solares, seu consumo dietético se torna essencial quando a exposição solar é insuficiente para alcançar as necessidades diárias. Isso tem se tornado comum, particularmente entre pessoas residentes em centros urbanos que estão expostos a níveis subótimos de raios solares27,30,31 (Tabela 5).

 

 

Entretanto, são escassos os alimentos fonte de vitamina D, como a gema de ovo, fígado, manteiga e leite. Além disso, estes alimentos são atualmente pouco consumidos em função do elevado conteúdo de colesterol32. De modo geral, carnes e peixes magros têm apenas traços desta vitamina, estando as maiores concentrações presentes no arenque e na cavala16. Óleos de fígado de peixes como atum e linguado, bacalhau em particular e peixes como salmão, cavala, sardinha, enguia, arenque e atum são ricos em vitamina D19,33 (Tabela 6).

 

 

 

Outra fonte seriam os cogumelos, que naturalmente possuem pequenas quantidades de vitamina D, mas este alimento também não é freqüentemente consumido e está sujeito a grande variação sazonal no seu conteúdo de vitamina D32.

 

Infelizmente, a literatura é escassa em trabalhos envolvendo biodisponibilidade dessa vitamina. Alguns fatores dietéticos têm sido apontados como auxiliares ou redutores da biodisponibilidade da vitamina D. Porém, sabe-se que o leite ingerido conjuntamente com fontes naturais de vitamina D pode elevar de três a 10 vezes sua absorção, fato que pode ser explicado pela presença da lactoalbumina. Ácidos graxos de cadeia longa também facilitam a absorção de vitamina D, quando comparada a doses farmacológicas dessa vitamina. Já a ingestão de etanol e de fibras leva à diminuição da sua biodisponibilidade, pois promove perda biliar34.

Assim, a irradiação solar pode garantir o aporte de vitamina D na infância, mas com aumento do risco de câncer de pele; além disso, fontes alimentares desta vitamina são restritas. Sendo assim, uma opção mais segura de alcançar as necessidades dietéticas durante o crescimento seria o uso de suplementos dietéticos do tipo farmacêuticos ou o enriquecimento de alimentos com vitamina D27,35.

Consumo dietético de vitamina D

Estima-se que uma dieta saudável seja suficiente para alcançar plenitude em vitamina D, porém, como vimos antes, isso nem sempre acontece. Esta é a razão pela qual a deficiência de vitamina D tem se tornado freqüente em crianças e adolescentes em fase de crescimento nos EUA e Europa27,25.

Docio et al. realizaram um estudo para determinar níveis desejáveis de 25-OH-D3 em crianças e saber se elas mantêm estes níveis durante todo ano e verificaram que o limite mínimo para os níveis de 25-OH-D3 desejado em crianças é algo entre 12 e 20 ng/mL. Contudo, 31% das 51 crianças normais estudadas no inverno apresentaram níveis inferiores a 12 ng/mL, e 80% tiveram níveis abaixo de 20 ng/mL. Quando analisaram a dieta, encontraram consumo médio de 790±156 mg/dia de cálcio e 160±80 IU/dia de vitamina D, ambos abaixo do recomendado36.

Gordon et al. realizaram estudo em hospital urbano de Boston, no qual foi avaliada a prevalência de deficiência de vitamina D sérica em 307 adolescentes saudáveis. Foram encontrados 24,1% de pacientes deficientes em vitamina D, dos quais 4,6% estavam severamente deficientes. Estação do ano (inverno e primavera), etnia (afro-americanos), consumo de leite, índice de massa corporal (IMC) e atividade física foram fatores independentes e significativos de hipovitaminose D24.

Estudos com pré-adolescentes também demonstram deficiência nos níveis séricos e consumo de vitamina D. Rajakumar et al. avaliaram a proporção de deficiência de vitamina D em pré-adolescentes estadunidenses afro-descendentes de 6 a 10 anos. Quarenta e nove por cento apresentaram níveis séricos de 25-OH-D3 insuficientes (24±10,5 ng/mL). O consumo médio de vitamina D foi de 277±146 IU/dia, e 39% deles não atingiram o consumo diário adequado de vitamina D37.

No Brasil, até o presente momento, existem poucos estudos sobre prevalência de hipovitaminose D. O Rio Grande do Sul, devido às suas características climáticas, apresenta maior possibilidade de deficiência desta. Em um estudo realizado no Hospital de Clínicas de Porto Alegre (HCPA), Premaor & Furlanetto encontraram baixos níveis séricos de 25-OH-D3 nos pacientes internados nas equipes de medicina interna. Todavia, estes pacientes eram adultos e apresentavam vários fatores de risco para desenvolver a doença, portanto ainda não se conhece a extensão real deste distúrbio em nosso meio30.

 

Cálcio e vitamina D dietéticos no crescimento

Sendo assim, o decréscimo do consumo de cálcio e vitamina D em períodos de crescimento pode influenciar negativamente o desenvolvimento ósseo, causando não apenas raquitismo, que é o resultado final da deficiência de vitamina D, como também prejudicando o alcance da altura programada geneticamente25.

As necessidades de cálcio durante a puberdade e adolescência são maiores do que em qualquer outro período da vida, em função do acelerado desenvolvimento muscular, esquelético e endócrino11. O depósito mineral ósseo durante o crescimento puberal parece depender da absorção dietética de cálcio, assim como da redução da sua excreção, e isso depende de um adequado estado de vitamina D. Apesar disso, o entendimento da relação entre absorção de cálcio e vitamina D e crescimento é limitado38.

Abrams et al. compararam a altura de 315 meninas entre 5 e 15 anos com a absorção de cálcio dietético e encontraram relações positivas (r = 0,18; p = 0,001), demonstrando que um aumento na eficiência absortiva é, em parte, regulado para alcançar as necessidades do tamanho esquelético final. No entanto, esta relação permanece incerta, podendo ser devida a componentes genéticos ou a diferenças étnicas. Outra hipótese seria que a absorção de cálcio estivesse diretamente relacionada com a maior superfície intestinal dos indivíduos mais altos. Estes achados dependeram do estágio puberal independente da altura das meninas, pois foi observado um aumento na absorção de cálcio durante o início da puberdade38.

Prentice et al. avaliaram o efeito da suplementação com carbonato de cálcio (1.000 mg/dia) versus placebo em 143 meninos, entre 16 e 18 anos de idade, durante 13 meses, quanto à aquisição óssea e crescimento ósseo. A intervenção resultou em melhora no conteúdo mineral ósseo total, que aumentou 1,3% (p = 0,02), associada a incremento na altura de 0,4% (p = 0,0004) equivalente a 7 mm. Essa associação não foi encontrada em estudo com crianças menores e meninas na mesma faixa etária39. Apesar de existirem estudos com suplementação de cálcio, estudos relacionando cálcio dietético e crescimento são escassos, assim como a vitamina D.

Os resultados de Black et al. confirmaram a visão de que crianças com longa história de baixo consumo de leite têm baixa ingestão de cálcio dietético (443±230 mg/dia) e pobre saúde óssea (conteúdo mineral ósseo 0,45 g menor; p < 0,01) em comparação com crianças que consomem leite. Isso também reforça a hipótese de que crianças que não consomem leite de vaca têm estatura menor que aquelas que consomem leite regularmente (0,65 cm menores; p < 0,01). Além desses resultados, o escore z para conteúdo mineral ósseo total correlacionou-se positivamente com o consumo dietético de cálcio (r = 0,38; p < 0,006). Neste estudo, o consumo dietético de cálcio das crianças que não consomem leite não alcançou a grande quantidade de cálcio necessária para demanda de crescimento puberal40.

 

Conclusões

Assim, podemos concluir que, durante o crescimento, o suprimento adequado de cálcio e vitamina D é considerado criticamente importante no desenvolvimento ósseo e, se a criança está apta a alcançar seu potencial genético de crescimento e pico de massa óssea, a dieta deve ter quantidade suficiente destes nutrientes. Também ficou claro o baixo consumo dietético de cálcio e vitamina D entre crianças e adolescentes, e que este causa efeito deletério na saúde esquelética e metabolismo ósseo. É necessário investigar as causas da baixa ingestão de cálcio e vitamina D entre indivíduos no período de crescimento, como na infância e na adolescência, estabelecer estratégias nutricionais para aumentar seu consumo dietético e propiciar o alcance de alimentos ricos nestes nutrientes entre as populações em risco nutricional.

 

Agradecimentos

Agradecemos aos funcionários, residentes e pós-graduandos do Ambulatório de Baixa Estatura do Serviço de Endocrinologia do HCPA pelo seu auxílio em diversas fases de nosso trabalho. Também somos gratos ao Fundo de Incentivo à Pesquisa e Eventos (FIPE) do HCPA, à Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) e ao Centro de Endocrinologia e Diabetes do Rio Grande do Sul (CEDERS) pelo suporte financeiro para o desenvolvimento de vários projetos.

 

Referências

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2. Hall R, Anderson J, Stuart GA, Besser GM. Clinical Endocrinology. 2nd ed. 1994.         [ Links ]

3. Giugliani ER. Baixa estatura: um mal da sociedade brasileira. J Pediatr (Rio J). 1994;70:261.         [ Links ]

4. Larsen PR, Kronenberg H, Melmed S, et. al. Willians textbook of endocrinology, 10ed. Phyladelphia.: Elsevier.; 2003.         [ Links ]

5. Cowell CT. Short stature. In: Brook CG, Hindmarsh PC, editors. Clinical pediatric endocrinology. 3th ed. Cambridge: Blackwell Science; 1996. p. 136-72.         [ Links ]

6. Onis M, Blössner M. The World Health Organization Global Database on Child Growth and Malnutrition: methodology and applications. Int J Epidemiol. 2003;32:518-26.         [ Links ]

7. Aerts D, Drachler ML, Giugliani ER. Determinants of growth retardation in Southern Brazil. Cad Saude Publica. 2004;20:1182-90.         [ Links ]

8. Singh M. Role of micronutrients for physical growth and mental development. Indian J Pediatr. 2004;71:59-62.         [ Links ]

9. Holick MF. Resurrection of Vitamin D deficiency and rickets. J Clin Invest. 2006; 116:2062-72.         [ Links ]

10. Cobayashi F. Cálcio: seu papel na nutrição e saúde. Compacta Nutr. 2004;2:3-18.         [ Links ]

11. Joint FAO/WHO Expert Consultation on Human vitamin and mineral requirements. Bangkok; 1998.         [ Links ]

12. Branca F, Valtueña S. Calcium, physical activity and bone health – building bones for a stronger future. Public Health Nutr. 2001;4:117-23.         [ Links ]

13. Flynn A. The role of dietary calcium in bone health. Proc Nutr Soc. 2003;62:851-8.         [ Links ]

14. Grüdtner VS, Weingrill P, Fernandes AL. Aspectos da absorção no metabolismo do cálcio e vitamina D. Rev. Bras. Reumatol. 1997;37:143-51.         [ Links ]

15. Food and Nutrition Board and Institute of Medicine. Dietary reference intakes for calcium, phosphorus, magnesium, vitamin D, and fluoride. Washington, DC: National Academy Press; 2002.         [ Links ]

16. Lopez FA, Brasil AD. Nutrição e dietética em clínica pediátrica. São Paulo: Atheneu; 2004.         [ Links ]

17. Medeiros LC, Speridião PG, Sdepanian VL, Fagundes-Neto U, Morais MB. Ingestão de nutrientes e estado nutricional de crianças em dieta isenta de leite de vaca e derivados. J Pediatr (Rio J). 2004;80:363-70.         [ Links ]

18. Vitolo MR. Nutrição: da gestação à adolescência. Rio de Janeiro: Reichmann & Affonso; 2003.         [ Links ]

19. Tabela brasileira de composição de alimentos/NEPA-UNICAMP. 2a ed. Campinas, SP: NEPA-UNICAMP; 2006.         [ Links ]

20. Pinheiro AB, Lacerda SE, Benzecry EH. Tabela para avaliação de consumo alimentar em medidas caseiras. 4a ed. São Paulo: Atheneu; 2002.         [ Links ]

21. Rajeshwari R, Nicklas TA, Yang SJ, Berenson GS. Longitudinal changes in intake and food sources of calcium from childhood to young adulthood: The Bogalusa Heart Study. J Am Coll Nutr. 2004;23:341-50.         [ Links ]

22. Salamoun MM, Kizirian AS, Tannous RI, Nabulsi MM, Choucair MK, Deeb ME, et al. Low calcium and vitamin D intake in healthy children and adolescents and their correlates. Eur J Clin Nutr. 2005;59:177-84.         [ Links ]

23. Lerner BR, Lei DL, Chaves SP, Freire RD. O cálcio consumido por adolescentes de escolas públicas de Osasco, São Paulo. Rev Nutr. 2000;13:57-63.         [ Links ]

24. Gordon CM, DePeter KC, Feldman HA, Grace E, Emans SJ. Prevalence of vitamin D deficiency among healthy adolescents. Arch Pediatr Adolesc Med. 2004;158:531-7.         [ Links ]

25. Holick MF. Sunlight and vitamin D for bone health and prevention of autoimmune diseases, cancers and cardiovascular disease. Am J Clin Nutr. 2004;80:1678S-88S.         [ Links ]

26. Holick MF. Vitamin D deficiency. N Engl J Med. 2007;357:266-81.         [ Links ]

27. Hochberg Z. Vitamin D and rickets. Consensus development for the supplementation of vitamin D in childhood and adolescence. Endocr Dev Basel. 2003;6:259-81.         [ Links ]

28. Molgaart C, Michaelsen KF. Vitamin D and bone health in early life. Proc Nutr Soc. 2003;62:823-8.         [ Links ]

29. Greer FR. Issues in establishing vitamin D recommendations for infants and children. Am J Clin Nutr. 2004;80:1759S-62S.         [ Links ]

30. Premaor MO, Furlanetto TW. Hipovitaminose D em adultos: entendendo melhor a apresentação de uma velha doença. Arq Bras Endocrinol Metab. 2006;50:25-37.         [ Links ]

31. Ladhani S, Srinivasan L, Buchanan C, Allgrove J. Presentation of vitamin D deficiency. Arch Dis Child. 2004;89:781-4.         [ Links ]

32. Calvo MS, Whiting SJ. Public Health Strategies to overcome barriers to optimal vitamin D status in population with special needs. J Nutr. 2006;136:1135-9.         [ Links ]

33. United States Department of Agriculture. USDA National Nutrient Database for Standard Reference, Release 19. http://www.ars.usda.gov/nutrientdata. Access: 02.09.2007.         [ Links ]

34. Mourão DM, Sales NS, Coelho SB, Pinheiro-Santana HM. Biodisponibilidade de vitaminas lipossolúveis. Rev Nutr. 2005;18:529-39.         [ Links ]

35. Newmark HL, Heaney RP, Lachance PA. Should calcium and vitamin D added to the current enrichment program for cereal-grain products? Am J Clin Nutr. 2004; 80:264-70.         [ Links ]

36. Docio S, Riancho JA, Pérez A, Olmos JM, Amado JA, González-macías J. Seasonal deficiency of vitamin D in children: a potential target for osteoporosis-preventing strategies? J Bone miner Res. 1998;13:544-8.         [ Links ]

37. Rajakumar K, Fernstrom JD, Janosky JE, Greenspan SL. Vitamin D Insufficiency in Preadolescent African-American Children. Clin Pediatr (Phila). 2005;44:683-92.         [ Links ]

38. Abrams AS, Griffin IJ, Hawthorne KM, Liang L. Height and height Z-score are related to calcium absorption in five to fifteen year-old girls. J Clin Endocrinol Metab. 2005;90:5077-81.         [ Links ]

39. Prentice A, Ginty F, Stear SJ, Jones SC, Laskey MA, Cole TJ. Calcium suplementation increases stature and bone mineral mass of 16- to 18-year-old boys. J Clin Endocrinol Metab. 2005;90:3153-61.         [ Links ]

40. Black RE, Williams SM, Jones IE, Goulding A. Children who avoid drinking cow milk have low dietary calcium intakes and poor bone health. Am J Clin Nutr. 2002;76:675-80.         [ Links ]

 

 

Correspondência:
Mauro A. Czepielewski
Serviço de Endocrinologia
Hospital de Clínicas de Porto Alegre
Rua Ramiro Barcelos, 2350 – prédio 12/4º andar
CEP 90035-003 – Porto Alegre, RS
Tel.: (51) 3316.5600
Email:
maurocze@terra.com.br

Artigo submetido em 06.05.08, aceito em 14.05.08.
Não foram declarados conflitos de interesse associados à publicação deste artigo.

 

 

Como citar este artigo: Bueno AL, Czepielewski MA. The importance for growth of dietary intake of calcium and vitamin D. J Pediatr (Rio J). 2008;84(5):386-394.

 

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The Nutrition Source – Vitamin D and Health

The Nutrition Source

Vitamin D and Health

 

Table of Contents

Low Vitamin D: A Global Concern

The Institute of Medicine’s (IOM) recommended daily intake of vitamin D is 600 IU for people ages 1 to 70, and 800 IU after age 70. (7) Yet this is overly conservative, since the best available evidence shows optimal intakes are higher, at least 800–1,000 IU for adults.

In extremely high doses—hundreds of thousands of IU or more—vitamin D is toxic and can even cause death. But in children over the age of 9 and in adults, taking up to 4,000 IU per day as a supplement is safe; ages 4 to 8, up to 3,000 IU; ages 1 to 3, 2,500 IU; ages 6 to 12 months, up to 1,500 IU; and ages 0 to 6 months, up to 1,000 IU. (7)

Many people may need 2,000 IU per day (or more) for adequate blood levels, particularly if they have darker skin, spend winters at higher latitudes (such as the northern U.S.), or spend little time in the sun. If you fall into one of these groups, which would include most of the U.S. population, taking 2,000 IU is reasonable and well within the safe range for adults. As always, it’s a good idea to discuss use of supplements with your doctor, and he or she may want to order a vitamin D blood test.

To prevent rickets, the American Academy of Pediatrics recommends vitamin D supplements of 400 IU per day for breastfed infants, and also for non-breastfed infants and children who do not drink at least a liter of vitamin D fortified milk each day. (6)  Infants and children at high risk of deficiency—those who are born premature, have dark skin, or live at high latitudes—may need supplements of up to 800 IU per day, especially in the winter.

If you live north of the line connecting San Francisco to Philadelphia and Athens to Beijing, odds are that you don’t get enough vitamin D. The same holds true if you don’t get outside for at least a 15-minute daily walk in the sun. African-Americans and others with dark skin, as well as older individuals, tend to have much lower levels of vitamin D, as do people who are overweight or obese.

Worldwide, inadequate vitamin D is common, and deficiencies can be found on all continents, in all ethnic groups, and across all ages. Some surveys suggest that perhaps half of the world’s population has inadequate blood levels of vitamin D. (13)  Indeed, in industrialized countries, doctors are even seeing the resurgence of rickets, the bone-weakening disease that had been largely eradicated through vitamin D fortification. (46)

Why are these widespread low levels of vitamin D such a great concern? Because research conducted over the past decade suggests that vitamin D plays a much broader disease-fighting role than once thought.

Being “D-ficient” may increase the risk of a host of chronic diseases, such as osteoporosis, heart disease, some cancers, and multiple sclerosis, as well as infectious diseases, such as tuberculosis and even the seasonal flu.

Currently, there’s scientific debate about how much vitamin D people need each day. The Institute of Medicine (IOM), in a long-awaited report released in November 2010 recommends increasing the daily vitamin D intake for children and adults in the U.S. and Canada, to 600 IU per day for people ages 1 to 70, and 800 IU for people over age 70. (7) The report also recognized the safety of vitamin D by increasing the upper limit from 2,000 to 4,000 IU per day, and acknowledged that even at 4,000 IU per day, there was no good evidence of harm.

The new guidelines, however, are overly conservative about the recommended intake, and they do not give enough weight to some of the latest science on vitamin D and health. For bone health and chronic disease prevention, many people are likely to need more vitamin D than even these new government guidelines recommend.

 

Vitamin D Sources and Function

Vitamin D is both a nutrient we eat and a hormone our bodies make. Few foods are naturally rich in vitamin D, so the biggest dietary sources of vitamin D are fortified foods and vitamin supplements.

VITAMIN D FROM FOOD AND SUPLEMENTS

Very few foods naturally contain vitamin D. Good sources include dairy products and breakfast cereals (both of which are fortified with vitamin D), and fatty fish such as salmon and tuna.

For most people, the best way to get enough vitamin D is taking a supplement, but the level in most multivitamins (400 IU) is too low. Encouragingly, some manufacturers have begun adding 800 or 1,000 IU of vitamin D to their standard multivitamin preparations. If the multivitamin you take does not have 800 or 1,000 IU of vitamin D, you may want to consider adding a separate vitamin D supplement, especially if you don’t spend much time in the sun. Talk to your healthcare provider.

The body also manufactures vitamin D from cholesterol, through a process triggered by the action of sunlight on skin, hence its nickname, “the sunshine vitamin.”  Yet many people do not make enough vitamin D from the sun, among them, people who have a darker skin tone, who are overweight, who are older, and who cover up when they are in the sun. (1)

Correctly applied sunscreen reduces our ability to absorb vitamin D by more than 90 percent. (8) And not all sunlight is created equal: The sun’s ultraviolet B (UVB) rays—the so-called “tanning” rays, and the rays that trigger the skin to produce vitamin D—are stronger near the equator and weaker at higher latitudes. So in the fall and winter, people who live at higher latitudes (in the northern U.S. and Europe, for example) can’t make much if any vitamin D from the sun. (8)

 

Read more: what may increase your risk for low vitamin D

Vitamin D helps ensure that the body absorbs and retains calcium and phosphorus, both critical for building bone. Laboratory studies show that vitamin D can reduce cancer cell growth, can increase muscle strength and reduce falls in older people, and plays a critical role in controlling infections. Many of the body’s organs and tissues have receptors for vitamin D, and scientists are still teasing out its other possible functions.

 

New Vitamin D Research: Beyond Building Bones

Several promising areas of vitamin D research look far beyond vitamin D’s role in building bones. And, as you might expect, the news media release a flurry of reports every time another study links vitamin D to some new ailment. These reports can be confusing, however, because some studies are stronger than others, and any report needs to be interpreted in the light of all other evidence. More answers may come from randomized trials, such as the VITamin D and OmegA-3 TriaL (VITAL), which will enroll 20,000 healthy men and women to see if taking 2,000 IU of vitamin D or 1,000 mg of fish oil daily lowers the risk of cancer, heart disease, and stroke.

Here, we provide an overview of some of the more promising areas of vitamin D research, highlighting the complex role of vitamin D in disease prevention—and the many unanswered questions that remain.

 

Vitamin D and Bone and Muscle Strength

Vitamin D plays a definite role in bone health and reducing fractures; the central issue is, what is the minimum dose that is effective? Several randomized trials have shown that vitamin D supplementation prevents fractures—as long as it is taken in a high enough dose. (913)

 

NUTRITION IN-DEPTH

 

Why to Avoid Super High Doses of Vitamin D

A recent vitamin D trial drew headlines for its unexpected finding that a very high dose of vitamin D increased fracture and fall risk in older women. (18) The trial’s vitamin D dose—500,000 IU taken by mouth on a single day, once a year—was much higher than previously tested in an annual regimen.

There’s strong evidence that more moderate doses of vitamin D taken daily or weekly protect against fractures and falls—and are safe. Read more about this study’s findings, and why it makes sense to stick to more moderate vitamin D doses and avoid single, super high doses.

A summary of the evidence comes from a combined analysis of 12 fracture prevention trials that included more than 40,000 elderly people, most of them women. Researchers found that high intakes of vitamin D supplements—of about 800 IU per day—reduced hip and non-spine fractures by over 20 percent, while lower intakes (400 IU or less) failed to offer any fracture prevention benefit. (13)

Vitamin D may also help increase muscle strength, which in turn helps to prevent falls, a common problem that leads to substantial disability and death in older people. (1416)  Once again, vitamin D dose matters: A combined analysis of multiple studies found that taking 700 to 1,000 IU of vitamin D per day lowered the risk of falls by 19 percent, but taking 200 to 600 IU per day did not offer any such protection. (17)

Based on these fall- and fracture-prevention findings, the International Osteoporosis Foundation recommends that adults over age 60 aim for vitamin D blood levels of 30 ng/ml. (52) Most people will need vitamin D supplements of at least 800 to 1,000 IU per day, and possibly higher, to reach these levels.

 

Vitamin D and Heart Disease

The heart is basically a large muscle, and like skeletal muscle, it has receptors for vitamin D. (19) So perhaps it’s no surprise that studies are finding that inadequate vitamin D may be linked to heart disease. The Health Professional Follow-Up Study checked the vitamin D blood levels in nearly 50,000 men who were healthy, and then followed them for 10 years. (20) They found that men who were low in vitamin D were twice as likely to have a heart attack as men who had adequate levels of vitamin D. Other studies have found that low vitamin D levels were associated with higher risk of heart failure, sudden cardiac death, stroke, overall cardiovascular disease, and cardiovascular death. (2124) How exactly might vitamin D help prevent heart disease? There’s evidence that vitamin D plays a role in controlling blood pressure and preventing artery damage, and this may explain these findings. (25) Still, more research is needed before we can be confident of these benefits.

 

Vitamin D and Cancer

Nearly 30 years ago, researchers noticed an intriguing relationship between colon cancer deaths and geographic location: People who lived at higher latitudes, such as in the northern U.S., had higher rates of death from colon cancer than people who live closer to the equator. (26) The sun’s UVB rays are weaker at higher latitudes, and in turn, people’s vitamin D levels in these high latitude locales tend to be lower. This led to the hypothesis that low vitamin D levels might somehow increase colon cancer risk. (26)

 

Vitamin D and Geographic Location

Many scientific hypotheses about vitamin D and disease stem from studies that have compared solar radiation and disease rates in different countries. These can be a good starting point for other research but don’t provide the most definitive information…. Read more about vitamin D studies and geographic location.

Since then, dozens of studies suggest an association between low vitamin D levels and increased risks of colon and other cancers. (1,27)  The evidence is strongest for colorectal cancer, with observational studies consistently finding that the lower the vitamin D levels, the higher the risk is of these diseases. (2838) Vitamin D levels may also predict cancer survival, but evidence for this is still limited. (27) Yet finding such associations does not necessarily mean that taking vitamin D supplements will lower cancer risk.

The VITAL trial will look specifically at whether vitamin D supplements lower cancer risk. It will be years, though, before it releases any results. It could also fail to detect a real benefit of vitamin D, for several reasons: If people in the placebo group decide on their own to take vitamin D supplements, that could minimize any differences between the placebo group and the supplement group; the study may not follow participants for a long enough time to show a cancer prevention benefit; or study participants may be starting supplements too late in life to lower their cancer risk. In the meantime, based on the evidence to date, 16 scientists have circulated a “call for action” on vitamin D and cancer prevention: (27) Given the high rates of vitamin D inadequacy in North America, the strong evidence for reduction of osteoporosis and fractures, the potential cancer-fighting benefits of vitamin D, and the low risk of vitamin D supplementation, they recommend widespread vitamin D supplementation of 2,000 IU per day. (27) The

Canadian Cancer Society has also recommended that Canadian adults consider taking vitamin D supplements of 1,000 IU per day during the fall and winter; people who are at high risk of having low vitamin D levels (because they are older, have dark skin, spend little time in the sun, or cover up when they go outside) should consider taking supplements year round. (53)

 

Read more: vitamin D trials for cancer prevention

 

Vitamin D and Immune Function

Vitamin D’s role in regulating the immune system has led scientists to explore two parallel research paths: Does low vitamin D contribute to the development of multiple sclerosis, type 1 diabetes, and other so-called “autoimmune” diseases, where the body’s immune system attacks its own organs and tissues? And could vitamin D supplements help boost our body’s defenses to fight infectious disease, such as tuberculosis and seasonal flu? This is a hot research area and more findings will be emerging.

 

Vitamin D and Multiple Sclerosis: Multiple sclerosis (MS) rates are much higher far north (or far south) of the equator than in sunnier climes, and researchers suspect that chronic vitamin D inadequacy may be one reason why. One prospective study to look at this question found that among white men and women, those with the highest vitamin D blood levels had a 62 percent lower risk of developing MS than those with the lowest vitamin D levels. (39) The study didn’t find this effect among black men and women, most likely because there were fewer black study participants and most of them had low vitamin D levels, making it harder to find any link between vitamin D and MS if one exists.

 

Vitamin D and Type 1 Diabetes: Type 1 diabetes is another disease that varies with geography—a child in Finland is about 400 times more likely to develop it than a child in Venezuela. (40) Evidence that vitamin D may play a role in preventing type 1 diabetes comes from a 30-year study that followed more than 10,000 Finnish children from birth: Children who regularly received vitamin D supplements during infancy had a nearly 90 percent lower risk of developing type 1 diabetes than those who did not receive supplements. (41)  Other European case-control studies, when analyzed together, also suggest that vitamin D may help protect against type 1 diabetes. (42) No randomized controlled trials have tested this notion, and it is not clear that they would be possible to conduct.

 

Vitamin D, the Flu, and the Common Cold: The flu virus wreaks the most havoc in the winter, abating in the summer months. This seasonality led a British doctor to hypothesize that a sunlight-related “seasonal stimulus” triggered influenza outbreaks. (43) More than 20 years after this initial hypothesis, several scientists published a paper suggesting that vitamin D may be the seasonal stimulus. (44) Among the evidence they cite:

  • Vitamin D levels are lowest in the winter months. (44) 

  • The active form of vitamin D tempers the damaging inflammatory response of some white blood cells, while it also boosts immune cells’ production of microbe-fighting proteins. (44) 

  • Children who have vitamin D-deficiency rickets are more likely to get respiratory infections, while children exposed to sunlight seem to have fewer respiratory infections. (44) 

  • Adults who have low vitamin D levels are more likely to report having had a recent cough, cold, or upper respiratory tract infection. (45)

A recent randomized controlled trial in Japanese school children tested whether taking daily vitamin D supplements would prevent seasonal flu. (46) The trial followed nearly 340 children for four months during the height of the winter flu season. Half of the study participants received pills that contained 1,200 IU of vitamin D; the other half received placebo pills. Researchers found that type A influenza rates in the vitamin D group were about 40 percent lower than in the placebo group; there was no significant difference in type B influenza rates. This was a small but promising study, and more research is needed before we can definitively say that vitamin D protects against the flu. But don’t skip your flu shot, even if vitamin D has some benefit.

 

Vitamin D and Tuberculosis: Before the advent of antibiotics, sunlight and sun lamps were part of the standard treatment for tuberculosis (TB). (47) More recent research suggests that the “sunshine vitamin” may be linked to TB risk. Several case-control studies, when analyzed together, suggest that people diagnosed with tuberculosis have lower vitamin D levels than healthy people of similar age and other characteristics. (48)   Such studies do not follow individuals over time, so they cannot tell us whether low vitamin D levels led to the increased TB risk or whether taking vitamin D supplements would prevent TB. There are also genetic differences in the receptor that binds vitamin D, and these differences may influence TB risk. (49) Again, more research is needed. (49)

 

Vitamin D and Risk of Premature Death

A promising report in the Archives of Internal Medicine suggests that taking vitamin D supplements may even reduce overall mortality rates: A combined analysis of multiple studies found that taking modest levels of vitamin D supplements was associated with a statistically significant 7 percent reduction in mortality from any cause. (50) The analysis looked at the findings from 18 randomized controlled trials that enrolled a total of nearly 60,000 study participants; most of the study participants took between 400 and 800 IU of vitamin D per day for an average of five years. Keep in mind that this analysis has several limitations, chief among them the fact that the studies it included were not designed to explore mortality in general, or explore specific causes of death. More research is needed before any broad claims can be made about vitamin D and mortality. (51)

 

Why the IOM’s Vitamin D Recommendation Falls Short

Taken together, these disparate studies on bone health, heart disease, cancer, immune function, and early death add up to a powerful conclusion: Many people do not get enough vitamin D to protect their bones and minimize risk of falling—and taking vitamin D supplements of 1,000 to 2,000 IU per day would be a safe way to do both. This alone is good reason to consider taking a vitamin D supplement of 1,000 to 2,000 IU per day, and there is a strong likelihood of other benefits, even if not yet proven. Yet the IOM added up the evidence and reached a different conclusion—that children and most adults in the U.S. and Canada only need 600 IU of vitamin D a day. While the report notes that the 600 IU can come from food, supplements, or a combination of both, it acknowledges that very few Americans reach this intake.  Despite this, the committee recommended supplements for only a few special groups. There are several reasons why the IOM’s recommendation falls short:

 

Too Narrow a View of the Scientific Evidence

When evaluating the evidence on vitamin D, the IOM gave randomized clinical trials the most weight, since, in theory, such trials are the most rigorous: Researchers that randomly assign study participants to receive a treatment, such as a vitamin supplement, or a sugar pill (placebo), can be more certain that the treatment itself is responsible for any results.

But in reality, randomized clinical trials do not always offer the best evidence on vitamin supplements and health: They are expensive to conduct, so often they last only a few years, and they tend to enroll people who are already at a high risk of disease—for example, people who are older or who are not in the best health. As a result, these trials may be too short or too late in life to show the benefit of a vitamin supplement, if one exists.

Cohort studies can overcome some of the shortcomings of clinical trials, since they can follow large groups of initially-healthy people for long periods of time—long enough for links between vitamin levels and disease risks to emerge. Laboratory studies and animal studies also help fill in the research picture.
Most of the randomized trials of vitamin D have focused on bone health, and there’s been a lack of randomized trials on vitamin D and other chronic diseases. Unfortunately, the IOM committee interpreted this lack of trials as evidence of no benefit—in effect, ignoring the substantial evidence from cohort and other studies that vitamin D plays an important role in lowering the risk of several chronic diseases.

Based on this limited view, the IOM determined that most Americans have adequate blood levels of vitamin D—at least 20 nanograms per milliliter (ng/mL) or higher. Yet there’s much evidence that higher blood levels—on the order of 30 ng/mL—would do a better job of protecting bones, may help lower the risk of colon cancer and a host of diseases, and are safe. The safest and easiest way to achieve such blood levels is to take a supplement that contains at least 800 to 1,000 IU of vitamin D a day, and for people at high risk of low vitamin D levels, 2,000 IU a day.

 

Read more: why the IOM’s updated vitamin D and calcium guidelines are too low in vitamin D and too high in calcium for bone health

 

Too Hesitant on Vitamin D Supplements

Even if you accept the IOM’s lower criteria for adequate vitamin D blood levels (20 ng/mL)—and accept its findings that 600 IU of vitamin D per day is enough for most people to reach these blood levels—the report’s tepid recommendations on vitamin D supplements just do not make sense.

Q. What type of vitamin D is best?

Two forms of vitamin D are used in supplements: vitamin D2 (“ergocalciferol,” or pre-vitamin D) and vitamin D3 (“cholecalciferol”). Vitamin D3 is chemically indistinguishable from the form of vitamin D produced in the body…. Read more about what type of vitamin D is best.

 

The report recommends supplements for breastfed infants (and, especially, breastfed infants who have dark skin), since they are at high risk of deficiency. It also says that frail elderly who live in institutions should be monitored for vitamin D nutrition, and that a vitamin D “supplement is also an option” for people who do not eat dairy or animal products. But it does not explicitly advocate supplements for the population at large, or for other groups who are at risk of low vitamin D levels, such as people who are obese, who have dark skin, or who spend their winters in the northern states.

Yet data included with the IOM report, based on the National Health and Nutrition Examination Survey (which includes a representative sample of Americans), finds that 11 percent of European-Americans and 54 percent of African-Americans have blood vitamin D levels below 20 ng/mL. That means, in effect, that tens of millions of Americans have low vitamin D blood levels. These percentages would be even higher if one-third of Americans were not already taking vitamin D supplements in their multivitamins, and if the national survey had included winter samples from people living in the Northern states, since vitamin D levels are low at that time of year.

Very few Americans get the recommended 600 IU of vitamin D per day from food alone. The IOM committee acknowledges this—yet still concludes that Americans meet “average requirements” for vitamin D.  (Even the rationale for recommending 600 IU per day to achieve the low bar of 20 ng/mL is based on a flawed analysis by the IOM committee that considered the average blood level for a population; if the average is at 20 ng/mL, half of the population will be below that level. )

So how are Americans getting their vitamin D? The committee speculates that people get “at least some vitamin D from inadvertent or deliberate sun exposure.” Unprotected sun exposure, though, can increase the risk of skin cancer, and generally, it’s not recommended as a way to obtain vitamin D. Given that, it does not make sense for the committee to recommend a vitamin D intake that most people cannot get through food—while at the same time, giving only minimal guidance on who might really need vitamin D supplements.

 

Overstated Concern about High Vitamin D Blood Levels

In addition to understating the potential benefits of vitamin D and the need for supplements, the IOM overstated the concerns about having too-high blood levels of vitamin D.  For example, when the IOM committee looked at the relationship between vitamin D blood levels and premature death, it focused on data showing that at very high vitamin D blood levels—upwards of 70 ng/mL—mortality rates rise slightly. It glossed over data showing that mortality rates steadily drop as vitamin D levels rise, at least up to 40 ng/mL, and perhaps beyond: Since relatively few people have vitamin D levels higher than 40 ng/mL, there is not as much mortality data for levels in the 40–70 ng/mL range. Most studies suggest mortality continues to decrease—or does not increase—in the 40–70 ng/mL range, but a few studies have shown an increased mortality within this range.

As if to further justify its cautionary tone on vitamin D, the IOM’s press release pointed to other vitamin supplements—antioxidants like beta carotene and vitamin E, for example—that initially seemed promising for disease prevention but failed to pan out (and, sometimes, seemed to cause harm) in clinical trials. (54) Here too, though, the IOM’s logic is flawed: Beta carotene and vitamin E trials tested extremely high doses of those vitamins—ten to twenty times higher than what one might naturally get from a healthy diet. Vitamin D, though, is a different story: Spending a short time in the summer sun can produce the equivalent of 10,000 IU or more of vitamin D, and our evolutionary ancestors (who spent more time outdoors than we do, with less clothing) surely had much higher vitamin D levels than we typically have now.  By comparison, a vitamin D supplement of 1,000 to 2,000 IU a day is a very modest dose, and may be lower than optimal.

 

The Bottom Line: Many People Need Extra Vitamin D

Based on the evidence to date, it’s clear that many people don’t get enough vitamin D to protect their health. The International Osteoporosis Federation’s vitamin D recommendations, (52) though developed to prevent fall and fractures in older adults, offer a solid, evidence-based guidepost for younger and middle-aged adults, too: Taking a vitamin D supplement of 800 to 1,000 IU per day will help people, on average, achieve adequate blood levels of vitamin D (30 ng/mL). These vitamin D amounts are safe, falling well below the newly raised vitamin D upper limit of 4,000 IU per day—and they are easy to achieve, since more and more multivitamins now contain 800 to 1,000 IU of vitamin D. If your vitamin contains only 400 IU of vitamin D, consider adding an extra vitamin D supplement. People who are at high risk of deficiency, including people with darker skin, who are obese, or who spend little time in the sun, may need 2,000 IU of vitamin D (or more) to achieve adequate levels in the blood. If you fall into one of these groups, taking 2,000 IU of vitamin D each day is reasonable—and it’s an amount that falls well within the safe range. As always, it’s a good idea to discuss use of supplements with your doctor, and he or she may want to order a vitamin D blood test.

What makes the most sense from a public health point of view? It would be expensive to test everyone’s vitamin D blood levels, especially since the tests would need to be repeated seasonally. While people can make vitamin D from the sun, getting too much sun increases the risk of skin cancer, so it’s just not the best way to get vitamin D. By comparison, vitamin D supplements of 800 to 1,000 IU per day are inexpensive and safe—and provide a reasonable approach to avoiding D-ficiency.

 

References

1. Holick MF. Vitamin D deficiency. N Engl J Med. 2007; 357:266-81.

2. Gordon CM, DePeter KC, Feldman HA, Grace E, Emans SJ. Prevalence of vitamin D deficiency among healthy adolescents. Arch Pediatr Adolesc Med. 2004; 158:531-7.

3. Lips P. Worldwide status of vitamin D nutrition. J Steroid Biochem Mol Biol. 2010; 121:297-300.

4. Robinson PD, Hogler W, Craig ME, et al. The re-emerging burden of rickets: a decade of experience from Sydney. Arch Dis Child. 2006; 91:564-8.

5. Kreiter SR, Schwartz RP, Kirkman HN, Jr., Charlton PA, Calikoglu AS, Davenport ML. Nutritional rickets in African American breast-fed infants. J Pediatr. 2000; 137:153-7.

6. Misra M, Pacaud D, Petryk A, Collett-Solberg PF, Kappy M. Vitamin D deficiency in children and its management: review of current knowledge and recommendations. Pediatrics. 2008; 122:398-417.

7. Institute of Medicine. Dietary Reference Intakes for Calcium and Vitamin D. Washington, D.C.: National Academies Press, 2010.

8. Holick MF. Vitamin D: importance in the prevention of cancers, type 1 diabetes, heart disease, and osteoporosis. Am J Clin Nutr. 2004; 79:362-71.

9. Boonen S, Lips P, Bouillon R, Bischoff-Ferrari HA, Vanderschueren D, Haentjens P. Need for additional calcium to reduce the risk of hip fracture with vitamin d supplementation: evidence from a comparative metaanalysis of randomized controlled trials. J Clin Endocrinol Metab. 2007; 92:1415-23.

10. Bischoff-Ferrari HA, Willett WC, Wong JB, Giovannucci E, Dietrich T, Dawson-Hughes B. Fracture prevention with vitamin D supplementation: a meta-analysis of randomized controlled trials. JAMA. 2005; 293:2257-64.

11. Cauley JA, Lacroix AZ, Wu L, et al. Serum 25-hydroxyvitamin D concentrations and risk for hip fractures. Ann Intern Med. 2008; 149:242-50.

12. Cauley JA, Parimi N, Ensrud KE, et al. Serum 25 HydroxyVitamin D and the Risk of Hip and Non-spine Fractures in Older Men. J Bone Miner Res. 2009.

13. Bischoff-Ferrari HA, Willett WC, Wong JB, et al. Prevention of nonvertebral fractures with oral vitamin D and dose dependency: a meta-analysis of randomized controlled trials. Arch Intern Med. 2009; 169:551-61.

14. Bischoff-Ferrari HA, Dawson-Hughes B, Willett WC, et al. Effect of Vitamin D on falls: a meta-analysis. JAMA. 2004; 291:1999-2006.

15. Broe KE, Chen TC, Weinberg J, Bischoff-Ferrari HA, Holick MF, Kiel DP. A higher dose of vitamin D reduces the risk of falls in nursing home residents: a randomized, multiple-dose study. J Am Geriatr Soc. 2007; 55:234-9.

16. Bischoff-Ferrari HA, Orav EJ, Dawson-Hughes B. Effect of cholecalciferol plus calcium on falling in ambulatory older men and women: a 3-year randomized controlled trial. Arch Intern Med. 2006; 166:424-30.

17. Bischoff-Ferrari HA, Dawson-Hughes B, Staehelin HB, et al. Fall prevention with supplemental and active forms of vitamin D: a meta-analysis of randomised controlled trials. BMJ. 2009; 339:b3692.

18. Sanders KM, Stuart AL, Williamson EJ; et al. Annual high-dose oral vitamin D and falls and fractures in older women: a randomized controlled trial. JAMA. 2010;303:1815-1822.

19. Giovannucci E. Expanding roles of vitamin D. J Clin Endocrinol Metab. 2009; 94:418-20.

20. Giovannucci E, Liu Y, Hollis BW, Rimm EB. 25-hydroxyvitamin D and risk of myocardial infarction in men: a prospective study. Arch Intern Med. 2008; 168:1174-80.

21. Pilz S, Marz W, Wellnitz B, et al. Association of vitamin D deficiency with heart failure and sudden cardiac death in a large cross-sectional study of patients referred for coronary angiography. J Clin Endocrinol Metab. 2008; 93:3927-35.

22. Pilz S, Dobnig H, Fischer JE, et al. Low vitamin D levels predict stroke in patients referred to coronary angiography. Stroke. 2008; 39:2611-3.

23. Wang TJ, Pencina MJ, Booth SL, et al. Vitamin D deficiency and risk of cardiovascular disease. Circulation. 2008; 117:503-11.

24. Dobnig H, Pilz S, Scharnagl H, et al. Independent association of low serum 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D levels with all-cause and cardiovascular mortality. Arch Intern Med. 2008; 168:1340-9.

25. Holick MF. The vitamin D deficiency pandemic and consequences for nonskeletal health: mechanisms of action. Mol Aspects Med. 2008; 29:361-8.

26. Garland CF, Garland FC. Do sunlight and vitamin D reduce the likelihood of colon cancer? Int J Epidemiol. 1980; 9:227-31.

27. Garland CF, Gorham ED, Mohr SB, Garland FC. Vitamin D for cancer prevention: global perspective. Ann Epidemiol. 2009; 19:468-83.

28. Yin L, Grandi N, Raum E, Haug U, Arndt V, Brenner H. Meta-analysis: longitudinal studies of serum vitamin D and colorectal cancer risk. Aliment Pharmacol Ther. 2009; 30:113-25.

29. Wu K, Feskanich D, Fuchs CS, Willett WC, Hollis BW, Giovannucci EL. A nested case control study of plasma 25-hydroxyvitamin D concentrations and risk of colorectal cancer. J Natl Cancer Inst. 2007; 99:1120-9.

30. Gorham ED, Garland CF, Garland FC, et al. Optimal vitamin D status for colorectal cancer prevention: a quantitative meta analysis. Am J Prev Med. 2007; 32:210-6.

31. Giovannucci E. Epidemiological evidence for vitamin D and colorectal cancer. J Bone Miner Res. 2007; 22 Suppl 2:V81-5.

32. Lin J, Zhang SM, Cook NR, Manson JE, Lee IM, Buring JE. Intakes of calcium and vitamin D and risk of colorectal cancer in women. Am J Epidemiol. 2005; 161:755-64.

33. Huncharek M, Muscat J, Kupelnick B. Colorectal cancer risk and dietary intake of calcium, vitamin D, and dairy products: a meta-analysis of 26,335 cases from 60 observational studies. Nutr Cancer. 2009; 61:47-69.

34. Bertone-Johnson ER, Chen WY, Holick MF, et al. Plasma 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D and risk of breast cancer. Cancer Epidemiol Biomarkers Prev. 2005; 14:1991-7.

35. Garland CF, Gorham ED, Mohr SB, et al. Vitamin D and prevention of breast cancer: pooled analysis. J Steroid Biochem Mol Biol. 2007; 103:708-11.

36. Lin J, Manson JE, Lee IM, Cook NR, Buring JE, Zhang SM. Intakes of calcium and vitamin D and breast cancer risk in women. Arch Intern Med. 2007; 167:1050-9.

37. Robien K, Cutler GJ, Lazovich D. Vitamin D intake and breast cancer risk in postmenopausal women: the Iowa Women’s Health Study. Cancer Causes Control. 2007; 18:775-82.

38. Freedman DM, Chang SC, Falk RT, et al. Serum levels of vitamin D metabolites and breast cancer risk in the prostate, lung, colorectal, and ovarian cancer screening trial. Cancer Epidemiol Biomarkers Prev. 2008; 17:889-94.

39. Munger KL, Levin LI, Hollis BW, Howard NS, Ascherio A. Serum 25-hydroxyvitamin D levels and risk of multiple sclerosis. JAMA. 2006; 296:2832-8.

40. Gillespie KM. Type 1 diabetes: pathogenesis and prevention. CMAJ. 2006; 175:165-70.

41. Hypponen E, Laara E, Reunanen A, Jarvelin MR, Virtanen SM. Intake of vitamin D and risk of type 1 diabetes: a birth-cohort study. Lancet. 2001; 358:1500-3.

42. Zipitis CS, Akobeng AK. Vitamin D supplementation in early childhood and risk of type 1 diabetes: a systematic review and meta-analysis. Arch Dis Child. 2008; 93:512-7.

43. Hope-Simpson RE. The role of season in the epidemiology of influenza. J Hyg (Lond). 1981; 86:35-47.

44. Cannell JJ, Vieth R, Umhau JC, et al. Epidemic influenza and vitamin D. Epidemiol Infect. 2006; 134:1129-40.

45. Ginde AA, Mansbach JM, Camargo CA, Jr. Association between serum 25-hydroxyvitamin D level and upper respiratory tract infection in the Third National Health and Nutrition Examination Survey. Arch Intern Med. 2009; 169:384-90.

46. Urashima M, Segawa T, Okazaki M, Kurihara M, Wada Y, Ida H. Randomized trial of vitamin D supplementation to prevent seasonal influenza A in schoolchildren. Am J Clin Nutr. 2010 91:1255-60. Epub 2010 Mar 10.

47. Zasloff M. Fighting infections with vitamin D. Nat Med. 2006; 12:388-90.

48. Nnoaham KE, Clarke A. Low serum vitamin D levels and tuberculosis: a systematic review and meta-analysis. Int J Epidemiol. 2008; 37:113-9.

49. Chocano-Bedoya P, Ronnenberg AG. Vitamin D and tuberculosis. Nutr Rev. 2009; 67:289-93.

50. Autier P, Gandini S. Vitamin D supplementation and total mortality: a meta-analysis of randomized controlled trials. Arch Intern Med. 2007; 167:1730-7.

51. Giovannucci E. Can vitamin D reduce total mortality? Arch Intern Med. 2007; 167:1709-10.

52. Dawson-Hughes B, Mithal A, Bonjour JP,  et al. IOF position statement: vitamin D recommendations for older adults. Osteoporos Int. 2010. 21:1151-4.

53. Canadian Cancer Society.  Canadian Cancer Society Announces Vitamin D Recommendation. 2007. Accessed March 24, 2011.

54. National Academies. Press Release: IOM Report Sets New Dietary Intake Levels for Calcium and Vitamin D To Maintain Health and Avoid Risks Associated With Excess. November 30, 2010. Accessed March 24, 2011.

Fonte

http://www.hsph.harvard.edu/nutritionsource/what-should-you-eat/vitamin-d/#vitamin-d-recommendations

http://www.hsph.harvard.edu/nutritionsource/what-should-you-eat/vitamin-d/

Folha de São Paulo: Terapia polêmica usa vitamina D em doses altas contra esclerose múltipla

Folha de São Paulo: Terapia polêmica usa vitamina D em doses altas contra esclerose múltipla

 

28/05/2012 — Celso Galli Coimbra

Ediçao de Domingo – 27/05/2012

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O vídeo referido na reportagem dominical da Folha está no endereço:

Vitamina D – Por uma outra terapia (Vitamin D – For an alternative therapy)

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DÉBORA MISMETTI
EDITORA-ASSISTENTE DE “CIÊNCIA+SAÚDE”

Há quase três anos o paulistano Daniel Cunha, 26, acordou com metade de seu rosto dormente. Foi trabalhar, voltou para casa e achou que a sensação ia passar. Não só não passou como piorou.

Foi ao hospital, fez exames e, depois de algumas consultas, recebeu o diagnóstico de esclerose múltipla. O mal é autoimune, causado pelo ataque ao revestimento dos neurônios pelo sistema imunológico da própria pessoa.

Desde 2010, Cunha abandonou o tratamento convencional, com injeções de interferon, remédio que controla a ação inflamatória da esclerose, mas causa efeitos colaterais como febre e mal-estar.

Ele passou a tomar todo dia uma dose alta de vitamina D, prescrita pelo neurologista Cícero Galli Coimbra, da Unifesp (Universidade Federal de São Paulo). O tratamento não é reconhecido pela maioria dos especialistas, que o consideram experimental.

Isso não impediu Cunha de usar a vitamina. Ele ficou tão satisfeito que realizou, com meios próprios e ajuda de amigos, um documentário de 30 minutos, disponível desde abril no YouTube (http://www.youtube.com/watch?v=erAgu1XcY-U), sobre a terapia.

No vídeo, com 18 mil acessos, pacientes de Coimbra falam sobre a vida antes e depois do novo tratamento, e o médico explica a relação entre a vitamina D e a doença.

 

                     Daniel Cunha, 26, autor de documentário sobre esclerose                    

 

HORMÔNIO

Produzida pelo corpo quando a pele fica exposta ao sol, a vitamina D na verdade é um hormônio, apesar de manter o nome consagrado.

É consenso há muito tempo que ela tem papel importante na mineralização dos ossos. “Experimentos vêm mostrando que ele age em vários outros tecidos, especialmente no sistema imunológico”, afirma a endocrinologista Marise Castro.

No caso da esclerose múltipla, pesquisas mostram que a prevalência da doença é mais alta em países distantes da linha do Equador, com incidência solar mais baixa, onde a população produz menos vitamina D.

Segundo Coimbra, a suplementação com o hormônio vem sendo testada desde os anos 1980 para reduzir os surtos de esclerose, períodos em que a doença pode deixar sequelas. Para ele, já há evidência suficiente de que as pessoas com a moléstia têm deficiência da vitamina.

“Desde 2003 venho cumprindo o dever ético de corrigir o problema metabólico desses pacientes. Todo médico tem a obrigação de fazer isso”, afirma o neurologista.

Até hoje, diz Coimbra, quase 900 pacientes com esclerose múltipla foram tratados. A maioria usa de 30 mil a 70 mil UI de vitamina D ao dia, mas alguns tomam 200 mil.

A dose ideal para a suplementação ainda é motivo de debate. Segundo Marise Castro, a quantidade usual é de 400 a 2.000 UI.

Mas, segundo Coimbra, essas doses não são realistas. “As pessoas com esclerose têm uma resistência genética à vitamina e precisam de doses mais altas.”

Os pacientes dele seguem uma dieta sem laticínios e fazem exames periódicos para controlar os níveis de cálcio na urina e no sangue. A vitamina D tem relação com o cálcio, e as doses altas podem causar cálculos renais.

“A intoxicação por vitamina D pode ser grave e leva meses para curar, porque ela se deposita no tecido adiposo”, diz a endocrinologista.

Coimbra rebate, citando um estudo que acompanhou pacientes com esclerose tomando vitamina D por sete meses, em doses crescentes, até chegar a 40 mil UI por dia.

Editoria de Arte/Folhapress

 

Para Maria Fernanda Mendes, membro-titular da Academia Brasileira de Neurologia, não há provas suficientes para receitar a terapia.

“Temos feito exames para dosar a vitamina e repô-la em caso de deficiência, até por conta da demanda dos pacientes, mas não é a recomendação oficial. Como há um tratamento comprovadamente melhor, esse só pode ser usado em pesquisas.”

Coimbra diz que não concorda com a realização de estudos controlados em que parte dos pacientes recebam a vitamina e parte, placebo.

“Alguém já fez estudo controlado sobre usar insulina para crianças diabéticas? Não, porque elas iam morrer. Se você tivesse uma filha com esclerose múltipla, que poderia ficar cega em um surto, correria o risco do placebo?”

Coimbra afirma que a relutância dos médicos em aceitar o tratamento vem dos conflitos de interesse com as farmacêuticas. “Há um interesse fabuloso no tratamento tradicional, que custa até R$ 11 mil por paciente por mês.”

O conflito de interesses foi um dos motivos que levou Daniel Cunha a fazer o documentário. “O tratamento com vitamina D me custa R$ 50 por mês. É a minha saúde, não é um leilão. Não me interessa se alguém vai ganhar dinheiro com isso. As pesquisas que todo mundo pede nunca vão sair, quem pagaria isso se não as farmacêuticas? Mas as pessoas não precisam ser reféns. A internet é nossa arma.”

Editoria de Arte/Folhapress

 

Fonte: http://www1.folha.uol.com.br/equilibrioesaude/1096497-terapia-polemica-usa-vitamina-d-em-doses-altas-contra-esclerose-multipla.shtml

Vídeos e textos sobre o assunto:

1.

Vitamina D pode revolucionar o tratamento da esclerose múltipla

http://biodireitomedicina.wordpress.com/2010/08/03/vitamina-d-pode-revolucionar-o-tratamento-da-esclerose-multipla/

 

2.

Vitamina D pode combater males que mais matam pessoas no mundo

http://biodireitomedicina.wordpress.com/2010/03/20/vitamina-d-pode-combater-males-que-mais-matam-pessoas-no-mundo/

 

3.

 

Informações médicas sobre a prevenção e tratamento de doenças neurodegenerativas e autoimunes, como Parkinson, Alzheimer, Lupus, Psoríase, Vitiligo, depressão

http://biodireitomedicina.wordpress.com/2011/03/23/informacoes-medicas-sobre-a-prevencao-e-tratamento-de-doencas-neurodegenerativas-e-auto-imunes-como-parkinson-alzheimer-lupus-psoriase-vitiligo-depressao/

 

4.                                       

 

Vitamina D – Por uma outra terapia

http://biodireitomedicina.wordpress.com/2012/04/12/vitamina-d-por-uma-outra-terapia/  

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-30.039254 -51.216930

 

http://biodireitomedicina.wordpress.com/2012/05/28/folha-de-sao-paulo-terapia-polemica-usa-vitamina-d-em-doses-altas-contra-esclerose-multipla/

Maior lobby no Congresso, ruralistas controlam 1/4 da Câmara

Maior lobby no Congresso, ruralistas controlam 1/4 da Câmara

João Fellet

Da BBC Brasil em Brasília

Atualizado em  24 de maio, 2012 – 14:07 (Brasília) 17:07 GMT

 

Com 120 deputados e 13 senadores, ruralistas são grupo mais poderoso do Congresso, dizem analistas

Responsáveis pelas maiores derrotas do governo no Congresso neste ano, os ruralistas cresceram desde a última legislatura, passando a controlar um quarto da Câmara.

A bancada, considerada por analistas o mais poderoso grupo de interesse no Parlamento brasileiro, vale-se de alianças com outras agremiações no Congresso para promover uma agenda que inclui, entre suas principais principais bandeiras, o perdão às dívidas de agricultores, a expansão de terras cultiváveis no país e a oposição à ampliação de Terras Indígenas.

Notícias relacionadas

Tópicos relacionados

O último grande embate do grupo com o governo ocorreu em abril, com a aprovação pela Câmara de uma versão do Código Florestal tida como favorável aos agricultores. Espera-se que a presidente Dilma Rousseff vete até o fim desta semana partes da legislação.

Segundo a Frente Parlamentar da Agropecuária (FPA), 120 deputados federais e 13 senadores integram a bancada ruralista, perfazendo 23,4% da Câmara e 16% do Senado. Os dados são próximos dos de levantamento feito em 2011 pelo Departamento Intersindical de Assessoria Parlamentar (DIAP), que apontou a existência de 120 deputados e 18 senadores ruralistas.

Na última legislatura (2007-2010), de acordo com o DIAP, 117 deputados federais pertenciam ao grupo (não há dados sobre senadores).

Embora não exista formalmente, a bancada ruralista agrega os parlamentares que, articulados, defendem no Congresso os pleitos do agronegócio. Grande parte de seus integrantes são donos de terra ou empresários dos setores alimentar e agroquímico.

Conquistas

A FPA afirma, porém, que a causa agrária conta com a simpatia de outros 77 deputados, que pertencem à frente mas não endossam todas as suas posições. Somando esses congressistas, a bancada diz influenciar ao menos 41% dos votos na Câmara.

 

Ruralistas são maior bancada do Congresso Nacional, perfazendo 23,4% da Câmara e 16% do Senado

O peso do grupo explica algumas de suas conquistas recentes: além de impor sua versão do Código Florestal, aprovou em comissão da Câmara, em março, uma PEC (Proposta de Emenda Constitucional) que transfere do Executivo ao Legislativo a prerrogativa de demarcar Terras Indígenas. Nesta terça-feira, a bancada aprovou ainda em subcomissão da Câmara a compra de terras por estrangeiros.

Nas três votações acima, o grupo se contrapôs a parlamentares ambientalistas, que integram a Frente Parlamentar Ambientalista. Ainda que seja mais numeroso que a frente agropecuária (com 247 deputados e 21 senadores) o grupo não tem conseguido fazer frente ao agrário.

Segundo especialistas, isso ocorre porque a maior parte dos congressitas que aderiu à frente o fez somente para simular interesse pelas causas ambientais, sem endossá-las na prática.

Derrota

A bancada ruralista, no entanto, foi derrotada em votação também nesta terça-feira sobre a PEC do Trabalho Escravo. Aprovada por 360 votos a 29, a medida prevê a expropriação de terras onde houver flagrante de exploração laboral. Os ruralistas tentaram esvaziar a votação, questionando a atual definição de trabalho escravo.

Segundo o historiador e assessor do Inesc (Instituto de Estudos Socioeconômicos) Edélcio Vigna, que estuda a bancada ruralista desde 2001, o resultado da votação mostra os limites da articulação do grupo.

Ele afirma que há na bancada “meia dúzia” de líderes, que definem as posições da agremiação e orientam as votações. “O êxito depende de essa meia dúzia chegar a um consenso, difundi-lo em nome da bancada e se articular com outros setores conservadores”, diz à BBC Brasil.

Na votação do Código Florestal, por exemplo, o grupo foi endossado por grande parte do PMDB, o partido mais representado na bancada ruralista e principal membro da base do governo no Congresso.

Influência e interesses

A agremiação tem ainda representantes em todas as bancadas estaduais do Congresso e em quase todos os partidos. E a influência do grupo, diz Vigna, vai além: controla a Comissão de Agricultura da Câmara e define o alto escalão do Ministério da Agricultura, hoje chefiado por Mendes Ribeiro (PMDB-RS).

“O ministro serve aos interesses da bancada dentro do Estado”, afirma.

O historiador afirma ainda que a influência do agronegócio no Congresso também se apoia no financiamento de campanhas eleitorais.

“Sabemos que há bancos, grandes empresas agroalimentares e agroquímicas financiando as campanhas de ruralistas. Queremos descobrir o que há por trás desse biombo”. Segundo Vigna, esses grupos exercem na bancada um poderoso lobby, atividade não regulamentada no país.

Já os ruralistas dizem representar interesses legítimos de um dos setores mais prósperos da economia brasileira. Eleito o próximo presidente da FPA, o deputado Homero Pereira (PR-MT) diz que o grupo busca garantir o direito de propriedade no campo, evitar a criação de parques sem indenização a donos de terra e combater a “tentativa de qualificar empregadores rurais como pessoas que exploram trabalho análogo à escravidão”.

Além disso, diz Pereira, a bancada está empenhada em garantir o uso integral das propriedades rurais. Hoje, a legislação define percentuais obrigatórios de preservação em terras privadas, que chegam a 80% para fazendas na Amazônia. “O proprietário paga impostos sobre 100% da terra e não pode mexer em 80% dela. É uma agressão”, afirma à BBC Brasil.

O deputado enaltece o desempenho do agronegócio brasileiro – “um dos poucos setores em que o Brasil consegue se inserir no mercado internacional” – e diz que o país tem “vocação e um potencial enorme para a produção de alimentos”.

Apesar do papel econômico que desempenham, afirma Pereira, os produtores rurais brasileiros não recebem o reconhecimento devido. “Como a sociedade brasileira se urbanizou rapidamente, as novas gerações perderam o ‘link’ com o meio rural. Mas o abastecimento da cidade se dá pelo campo e, diferentemente de outros países que concedem subsídios para o homem rural, aqui há um preconceito contra a atividade”.

 

http://www.bbc.co.uk/portuguese/noticias/2012/05/120524_ruralistas_abre_jf.shtml

 

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Para ONGs, Brasil perde liderança ambiental ao mudar Código Florestal

Para ONGs, Brasil perde liderança ambiental ao mudar Código Florestal

Daniel Gallas

 

Da BBC Brasil em Londres

 

Atualizado em  26 de abril, 2012 – 15:43 (Brasília) 18:43 GMT

Anistia a desmatamento do passado é uma das questões mais polêmicas do Congresso

Organizações ambientalistas internacionais afirmam que o Brasil pode estar perdendo a liderança no movimento ecológico global, depois que a Câmara dos Deputados aprovou na quarta-feira um novo texto que altera o Código Florestal brasileiro.

 

Em entrevista à BBC Brasil, representantes da WWF e do Greenpeace em Londres disseram que o Brasil sempre foi visto como um dos países mais ativos na promoção de ideias ambientais em fóruns internacionais, como as reuniões sobre mudanças climáticas da ONU. Mas, a aprovação do texto do deputado Paulo Piau (PMDB-MG) pode provocar uma mudança nessa percepção.

 

Notícias relacionadasMudança no Código Florestal ameaça liderança do Brasil, diz Marina SilvaBrasil precisará de ofensiva de comunicação para esclarecer ‘anistia’ ao desmatamentoRevisão do Código Florestal é aprovada

Tópicos relacionadosMeio Ambiente, BrasilO texto ainda precisa ser apreciado pela presidente Dilma Rousseff, que pode vetá-lo na íntegra ou parcialmente. Neste caso, a proposta volta para o Congresso, que pode fazer alterações ou derrubar o veto.

 

‘Choque’Entre os pontos mais polêmicos do parecer de Piau está a questão da anistia a produtores que desmataram florestas nas proximidades de rios.

 

O texto afeta os proprietários de terra que desmataram os 30 metros das Áreas de Preservação Permanente (APPs) nas margens de rios de até 10 metros de largura, segundo as normas estabelecidas em 1989. Eles ficam liberados da obrigação de recuperar totalmente a área degradada. De acordo com o texto aprovado por 274 votos a 189, os proprietários que infringiram tais regras terão de replantar apenas 15 metros.

 

“É um choque estarem alterando o Código Florestal que protege a floresta amazônica. Com a proximidade da Rio+20, isso bota muita pressão sobre a presidente Dilma Rousseff. Será muito difícil para ela se apresentar como defensora do ambiente”, disse à BBC Brasil Sarah Shoraka, ativista especialista em florestas do Greenpeace do Reino Unido.

 

“Durante a campanha ela [Dilma Rousseff] havia dito que não apoiaria nenhuma legislação que aumentasse o desmatamento e que desse anistia a criminosos, mas a proposta atual faz exatamente essas duas coisas. Agora é tudo uma questão da credibilidade dela, e o quanto ela está disposta a mudar”, disse.

 

“Agora é tudo uma questão da credibilidade dela [Dilma], e o quanto ela está disposta a muda.”

 

Sarah Shoraka, do Greenpeace em Londres

Para a diretora de Florestas da WWF no Reino Unido, Sandra Charity, a comunidade internacional está “perplexa” com a votação da quarta-feira no Congresso brasileiro.

 

“O Brasil tem uma trajetória de país moderno, que sempre esteve na liderança dos compromissos ambientais tendo em vista a sua posição na Conferência de Mudanças Climáticas de Copenhague [2009]. O país sempre esteve na frente e puxando os outros países. A aprovação deste texto é um retrocesso”, disse ela.

 

A representante da WWF ressalvou que o texto foi aprovado no Congresso, e não pela Presidência, mas que mesmo assim a medida tende a respingar na imagem do governo e do país como um todo.

 

‘Legado de Lula’Tanto a WWF e o Greenpeace dizem que o governo de Dilma Rousseff parece estar menos comprometido com ideias ambientalistas do que o do ex-presidente Lula.

 

“Nós estávamos acostumados com um Brasil que era líder no front ambiental. O ex-presidente Lula anunciou metas ambiciosas de redução de CO2 na em Copenhague”, disse Shoraka.

 

“Existe um descompasso entre o que a sociedade como um todo está esperando e pedindo e o que os dirigentes que fazem as leis estão decidindo.”

 

Sandra Charity, da WWF em Londres

Questionada se Dilma é menos preocupada com o ambiente do que Lula, afirmou: “Esta começando a dar essa impressão. O Código Florestal é o primeiro teste, mas se você olhar para outras tendências, como a aprovação de grandes hidrelétricas ou estradas sem os estudos de impacto ambiental corretos. É possível notar um padrão de valores ambientais se degradando no Brasil. Internacionalmente as pessoas estão de olho na Dilma agora. É o momento para ela provar que vai levar adiante o legado de Lula.”

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Dilma vai anunciar medida provisória tratando de trechos vetados do Código Florestal

 

Dilma vai anunciar medida provisória tratando de trechos vetados do Código Florestal

 

25/05/2012 – 14h10

 

senado, dilma rousseff, código florestal, medida, desmatamento

 

 

BRASÍLIA – Informação foi dada pelo senador Jorge Viana e segundo ele, haverá obrigação de se recompor as áreas desmatadas ilegalmente…

 

Agência Brasil

 

 foto: Antonio Cruz/ABr

 

Presidente Dilma Rousseff vai editar medida provisória sobre temas que serão vetados no Código Florestal Brasileiro

BRASÍLIA – O senador Jorge Viana (PT-AC) acaba de informar no Senado, no início da tarde desta sexta-feira (25), que a presidente Dilma Rousseff vai editar medida provisória sobre temas que serão vetados no Código Florestal Brasileiro aprovado pelo Congresso, entre esses, a anistia a produtores que desmataram áreas de preservação permanente. Haverá obrigação de se recompor as áreas desmatadas ilegalmente, segundo o senador.

 

Viana, que foi um dos relatores do Código Florestal no Senado, junto com o senador Luiz Henrique (PMDB-SC), esteve no final da manhã no Palácio do Planalto, onde recebeu a informação, a ser divulgada oficialmente apenas às 14 horas desta tarde, em entrevista coletiva com os ministros do Meio Ambiente, Izabella Teixeira, da Agricultura, Mendes Ribeiro, e do Desenvolvimento Agrário, Pepe Vargas.

 

“A presidente vai tirar do texto aprovado tudo que implicar em novos desmatamentos e em anistia aos produtores rurais que desmataram [áreas de preservação permanente]. Está mais do que na hora de virarmos a página da insegurança jurídica [com relação ao tema]”, disse o senador, referindo-se à decisão de editar medida provisória para preencher as lacunas legais geradas a partir do possível veto a trechos do Código Florestal.

 

De acordo com o senador, a medida provisória dará tratamento diferenciado a pequenos produtores e agricultores familiares com propriedades até 2 módulos rurais. Deve fazer parte da nova legislação, conforme Jorge Viana, a obrigação de recomposição ambiental das reservas que foram desmatadas ilegalmente. Também deve ser incluída na medida provisória a proibição a novos desmatamentos.

 

Segundo Jorge Viana, a medida provisória texto não incluirá anistia para os produtores rurais que desmataram área de preservação a partir de 2008, inviabilizando uma das principais mudanças obtidas pela bancada ruralista na aprovação do Código Florestal. Por conta da vitória ruralista, o texto aprovado pela Câmara, no fim de abril, deixou fora pontos que haviam sido negociados pelo governo durante a tramitação no Senado.

 

http://www.dci.com.br/dilma-vai-anunciar-medida-provisoria-tratando-de-trechos-vetados-do-codigo-florestal-id295852.html

 

 

Health Benefits of Omega 3 fatty acids

 

Health Benefits of Omega 3 fatty acids

Os benefícios do ômega 3

 

Health Benefits of Omega 3 fatty acids

Written by Gloria Tsang, RD
Published in Jul 2005; Updated in Mar 2010

(HealthCastle.com) What are omega 3 fatty acids? They’re a nutritional element that first caught researchers’ attention about 20 years ago – and what they discovered could have health benefits for anyone worried about a healthy heart.

In the early 1980s, studies showed that the Inuit had low rates of heart disease despite their high-fat diet rich in fish. It turns out the omega 3 fatty acids in the fish may be what protects their hearts, along with other health benefits.

Benefits of Omega 3 Fatty Acids in Heart Disease and Cholesterol

Omega 3 fatty acids are poly-unsaturated fatty acids. Studies show that a diet rich in omega 3 fatty acids may help lower triglycerides and increase HDL cholesterol (the good cholesterol). Omega 3 fatty acids may also act as an anticoagulant to prevent blood from clotting. Several other studies also suggest that these fatty acids may help lower high blood pressure.

Potential Benefits of Omega 3 Fatty Acids in Alzheimer’s

Omega 3 fatty acids may protect against the accumulation in the body of a protein believed to be linked to Alzheimer’s disease, according to the results of a new animal study published in the March 2005 issue of The Journal of Neuroscience. This study specifically investigated one particular kind of omega 3 fatty acids – Docosahexaenoic acid (DHA), and the results are encouraging.

Health Benefits of Omega 3 fatty acids

Written by Gloria Tsang, RD
Published in Jul 2005; Updated in Mar 2010

(HealthCastle.com) What are omega 3 fatty acids? They’re a nutritional element that first caught researchers’ attention about 20 years ago – and what they discovered could have health benefits for anyone worried about a healthy heart.

In the early 1980s, studies showed that the Inuit had low rates of heart disease despite their high-fat diet rich in fish. It turns out the omega 3 fatty acids in the fish may be what protects their hearts, along with other health benefits.

Benefits of Omega 3 Fatty Acids in Heart Disease and Cholesterol

Omega 3 fatty acids are poly-unsaturated fatty acids. Studies show that a diet rich in omega 3 fatty acids may help lower triglycerides and increase HDL cholesterol (the good cholesterol). Omega 3 fatty acids may also act as an anticoagulant to prevent blood from clotting. Several other studies also suggest that these fatty acids may help lower high blood pressure.

Potential Benefits of Omega 3 Fatty Acids in Alzheimer’s

Omega 3 fatty acids may protect against the accumulation in the body of a protein believed to be linked to Alzheimer’s disease, according to the results of a new animal study published in the March 2005 issue of The Journal of Neuroscience. This study specifically investigated one particular kind of omega 3 fatty acids – Docosahexaenoic acid (DHA), and the results are encouraging.

Omega 3: Fish or Plant?

With the increasing popularity of vegetarian diets and mounting fears about mercury and PCBs in seafood, people often ask about using flax oil (which contains alpha-linolenic acids – or ALA) instead of fish oil.

Our bodies can convert ALA into eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) – the beneficial elements of omega 3 – but the conversion process is slow. In addition, a high concentration of ALA (as present in flax oil pills) has been linked to higher risk of prostate cancer by some early research. Until more is known, men may be safest to choose fish oil for heart-healthy omega 3s instead of concentrated ALA.

http://www.healthcastle.com/omega3.shtml

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Vitamin D and the immune system: new perspectives on an old theme

Vitamin D and the immune system: new perspectives on an old theme

Martin Hewison, PhD

PUBMED CENTRAL Journal List – NIH Public Access – Autor Manuscript

———-

Journal List > NIHPA Author Manuscripts

Endocrinol Metab Clin North Am. Author manuscript; available in PMC 2011 June 1.

Published in final edited form as:
Endocrinol Metab Clin North Am. 2010 June; 39(2): 365–379.
doi:  10.1016/j.ecl.2010.02.010
PMCID: PMC2879394
NIHMSID: NIHMS180153
Copyright notice and Disclaimer

Vitamin D and the immune system: new perspectives on an old theme

Martin Hewison, PhD

Martin Hewison, Professor in Residence, Department of Orthopaedic Surgery and Molecular Biology Institute, David Geffen School of Medicine at UCLA, 615 Charles E. Young Drive South, Los Angeles, CA 90095, USA;
Corresponding author for proof and reprints: Martin Hewison, PhD, Department of Orthopaedic Surgery, David Geffen School of Medicine UCLA, 615 Charles E. Young Drive South, Los Angeles, CA 90095, USA, Tel: 310 206 1625, Fax: 310 825 5409, Email: mhewison@mednet.ucla.edu
The publisher’s final edited version of this article is available at Endocrinol Metab Clin North Am
See other articles in PMC that cite the published article.
Publisher’s Disclaimer
•  Other Sections▼
o Synopsis
o Introduction
o Vitamin D and innate immunity
o Vitamin D and adaptive immunity
o Vitamin D,  the immune system and human health
o Conclusions
o References

Synopsis
Interaction with the immune system is one of the most well-established non-classical effects of vitamin D. For many years this was considered to be a manifestation of granulomatous diseases such sarcoidosis, where synthesis of active 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) is known to be dysregulated. However, recent reports have supported a role for 1,25(OH)2D3 in mediating normal function of both the innate and adaptive immune systems. Crucially, these effects appear to be mediated via localized autocrine or paracrine synthesis of 1,25(OH)2D3 from precursor 25-hydroxyvitamin D3 (25OHD3), the main circulating metabolite of vitamin D. As such, the ability of vitamin D to influence normal human immunity will be highly dependent on the vitamin D status of individuals, and may lead to aberrant response to infection or autoimmunity in those who are vitamin D-insufficient. The potential health significance of this has been underlined by increasing awareness of impaired vitamin D status in populations across the globe. The following review article will describe in more detail some of the recent developments with respect to vitamin D and the immune system, together with possible clinical implications.
Keywords: vitamin D, CYP27b1, toll-like receptor, macrophage, cathelicidin, regulatory T-cells
o Vitamin D,  the immune system and human health

Introduction
Historical perspective
Non-classical actions of vitamin D were first recognized thirty years ago when receptors for active 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) were detected in various neoplastic cells lines 23,59. Other studies immediately following this showed that binding of 1,25(OH)2D3 to the vitamin D receptor (VDR) promoted antiproliferative and prodifferentiation responses in cancer cells 1,18, highlighting an entirely new facet of vitamin D action. The spectrum of non-classical responses to vitamin D was then extended to include actions on cells from the immune system 2,13. This interaction was further endorsed by the observation that some patients with the granulomatous disease sarcoidosis present with elevated circulating levels of 1,25(OH)2D3 and associated hypercalcemia 11,72. In these patients the high serum 1,25(OH)2D3 is due to increased activity of the enzyme 25-hydroxyvitamin D-1α-hydrooxylase (1α-hydroxylase). However, in contrast to normal subjects where 1α-hydroxylase is classically localized in the kidney, the increased synthesis of 1,25(OH)2D3 in patients with sarcoidosis involves 1α-hydroxylase activity in disease-associated macrophages 4,6,9. Thus, it was concluded that the immune system had the potential to both synthesize 1,25(OH)2D3 and elicit autocrine or paracrine responses from immune cells expressing the vitamin D receptor 38.
Despite these early advances, the precise nature of the interaction between vitamin D and the immune system remained unresolved for many years. Some pieces of the puzzle were easier to complete than others. For example, it became evident that dysregulation of 1,25(OH)2D3 was not restricted to sarcoidosis but was a common feature of many granulomatous disorders and some forms of cancer 39. Likewise, at least in vitro, it was possible to potently regulate a range of immune cell functions using 1,25(OH)2D3 or its synthetic analogs 35,97. However, the key remaining question concerned whether or not vitamin D could act as a physiological regulator of normal immune responses. Answers to this question began to appear about five years ago and new information on the fundamental nature of vitamin D sufficiency/insufficiency has provided a fresh perspective on non-classical actions of vitamin D. As a consequence, there is now a much broader acceptance that vitamin D plays an active role in regulating specific facets of human immunity. This will be detailed in the following review together with discussion on the possible impact of vitamin D insufficiency and vitamin D supplementation on normal immune function and human disease.
•  Other Sections▼
o Synopsis
o Introduction
o Vitamin D and innate immunity
o Vitamin D and adaptive immunity
o Vitamin D,  the immune system and human health
o Conclusions
o References

Vitamin D and innate immunity
Macrophages, vitamin D and cathelicidin
Consistent with the earlier seminal observations of extra-renal 1α-hydroxylase activity in patients with sarcoidosis, the effects of vitamin D on macrophage function have been central to many of the new observations implicating vitamin D in the regulation of immune responses. In common with natural killer cells (NK) and cytotoxic T-lymphocytes (cytotoxic T-cells), macrophages and their monocyte precursors play a central role in initial non-specific immune responses to pathogenic organisms or tissue damage – so called cell-mediated immunity. Their role is to phagocytose pathogens or cell debris and then eliminate or assimilate the resulting waste material. In addition, macrophages can interface with the adaptive immune system by utilizing phagocytic material for antigen presentation to T-lymphocytes (T-cells).

For many years, the key action of vitamin D on macrophages was thought to be its ability to stimulate differentiation of precursor monocytes to more mature phagocytic macrophages 1,2,45,93. This concept was supported by observations showing differential expression of VDR and 1α-hydroxylase during the differentiation of human monocytes macrophages 49. The latter report also emphasized early studies showing that normal human macrophages were able to synthesize 1,25(OH)2D3 when stimulated with interferon gamma (IFNγ) 46. Localized activation of vitamin D, coupled with expression of endogenous VDR was strongly suggestive of an autocrine or intracrine system for vitamin D action in normal monocytes/macrophages.

However, confirmation of such a mechanism was only obtained in 2006 when Robert Modlin and colleagues carried out DNA array analyses to define innate immunity genes that were specifically modulated in monocytes by Mycobacterium tuberculosis (M. tb). In a seminal investigation both the VDR and the gene for 1α-hydroxylase (CYP27B1) were shown to be induced following activation of the principal pathogen recognition receptor for M. tb, toll-like receptor 2/1 (TLR2/1) 56. Subsequent experiments confirmed that precursor 25OHD3 was able to induce intracrine VDR responses in monocytes that had been treated with a TLR2/1 activator. In particular, the TLR2/1–25OHD3 combination stimulated expression of the antibacterial protein cathelicidin, so that vitamin D was able to promote monocyte killing of M. tb 56. Notably, the ability to promote expression of the antibacterial protein following a TLR2/1 challenge was directly influenced by the 25OHD3 status of the donor serum used for monocyte culture 56. More recently, we have shown that vitamin D supplementation in vivo can also enhance TLR2/1-induced cathelicidin expression 5. Cathelicidin was identified several years ago as a target for transcriptional regulation by 1,25(OH)2D3-liganded VDR, in that its gene promoter contains a functional vitamin D response element (VDRE) 30,100. Interestingly, this VDRE occurs within a small interchangeable nuclear element (SINE) sequence which only appears to be present in the cathelicidin gene promoter of higher primates, suggesting that vitamin D regulation of this facet of innate immunity is a relatively recent evolutionary development 30.

Recent reports have underlined the importance of cathelicidin as a target for vitamin D but also suggest that this mechanism may be more complex than initially thought. As yet, the precise signal system by which TLR activation induces expression of VDR and 1α-hydroxylase remains unclear. Promoter-reporter analysis of the events involved in transcriptional regulation of CYP27B1 suggest that TLR4-mediated induction of the enzyme involves JAK-STAT, MAP kinase and nuclear factor kappB (NF-κB) pathways, and that these synergize with IFNγ-mediated induction of CYP27B192. However, other studies have proposed that TLR2/1 induction of 1α-hydroxylase occurs indirectly as a consequence of TLR2/1 induced interleukin-15 (IL-15) which is a potent inducer of CYP27B1 and 1α-hydroxylase activity 50. In a similar fashion, interleukin 17A (IL-17A) has been shown to enhance 1,25(OH)2D3-mediated induction of cathelicidin, although this response does not appear to involve transcriptional regulation of 1α-hydroxylase or increased VDR sensitivity 77. One pathway that has been poorly studied in this regard concerns the enzyme 24-hydroxylase, which is conventionally considered to function by inactivating 1,25(OH)2D3. The gene for 24-hydroxylase (CYP24) is potently induced by 25OHD3 following TLR2/1 activation of monocytes 56 but, as yet, it is unclear whether this involves the non-metabolic splice variant form of CYP24 known to be expressed by macrophages 82.

Regulation of the antibacterial protein by 1,25(OH)2D3 has been described for a wide variety of cell types other than macrophages, including keratinocytes 84,85,100, lung epithelial cells 104, myeloid cell lines 30,85,100 and placental trophoblasts 54. In some cases 54,84, this appears to involve an intracrine response similar to that reported for monocytes. However, the mechanisms controlling local synthesis of 1,25(OH)2D3 in these cells vary considerably. In keratinocytes, low baseline expression of 1α-hydroxylase is enhanced following epidermal wounding by transforming growth factor beta (TGFβ) 84. The resulting rise in 1,25(OH)2D3 concentrations upregulates expression of TLR2 and TLR4 by keratinocytes, thereby priming these cells for further innate immune responses to pathogens or tissue damage 84. By contrast, in trophoblasts, induction of cathelicidin and subsequent bacterial killing by 25OHD3 appears to be due to constitutive 1α-hydroxylase activity, which is not further enhanced by TLR activation 54. The latter may be due to the rapid non-immune induction of 1α-hydroxylase and VDR which occurs within the placenta during early gestation 24.

Although most of the studies of vitamin D-mediated innate immunity have focused on the role of 1,25(OH)2D3-bound VDR as a pivotal transcriptional regulator of cathelicidin, it is also important to recognize that other ligands may interact with the VDR 58. For example, recent studies of bilary epithelial cells have shown that cathelicidin expression can be induced in a VDR-dependent fashion by bile salts 19. This provides a mechanism for maintaining bilary sterility, although additive effects of 1,25(OH)2D3 also highlight a novel therapeutic application for vitamin D in the treatment of primary bilary cirrhosis. Conversely, other compounds may act to disrupt normal 1,25(OH)2D3-VDR-mediated immunity. The polycyclic aromatic hydrocarbon benzo(A)pyrene, a prominent product of cigarette smoking, has been shown to attenuate vitamin D-mediated induction of macrophage cathelcidin in a VDR-dependent fashion by stimulating expression of 24-hydroxylase, and vitamin D catabolism 64. The precise mechanism by which this occurs has yet to be determined but these data suggest that some toxic compounds are actively detrimental to vitamin D-mediated immunity.

The observations detailed above show clearly that vitamin D is a potent stimulator of mechanisms associated with pathogen elimination. In subsequent sections the clinical importance of this with respect to vitamin D insufficiency and immune-related diseases is discussed in more detail. However, one key question that immediately arises from the current observations is why there is a need to involve the vitamin D system in the TLR-induction of innate immunity. As previously described, VDR-mediated transcriptional regulation of cathelicidin is a relatively recent evolutionary change and was presumably advantageous when primates (including early Homo sapiens) were exposed to abundant sunlight, thereby priming high serum levels of vitamin D. Other benefits of incorporating vitamin D into innate immune regulation include the fact that it is associated with key feedback control pathways. As already mentioned, vitamin D has its own catabolic enzyme in the form of 24-hydroxylase which sensitively attenuates responses to 1,25(OH)2D3 and, in the case of the CYP24 splice variant, may also attenuate synthesis of this vitamin D metabolite 82. However, vitamin D may also provide feedback regulation of immune activation pathways in that 1,25(OH)2D3 has been shown to potently downregulate expression of monocyte TLR2 and TLR4, thereby suppressing inflammatory responses that are normally activated by these receptors 83. Thus, by utilizing both CYP24 and TLR regulatory mechanisms, vitamin D may help to promote appropriate innate immune responses whilst preventing an over-elaboration of innate immune responses and the tissue damage frequently associated with this.

Dendritic cells and antigen presentation

In addition to the phagocytic acquisition and elimination of pathogens and cell debris, innate immunity also involves the presentation of resultant antigen to cells involved in the adaptive arm of the immune system (see Figure 1). Although several cells are able to do this, the most well-recognized group of professional antigen presenting cells (APCs) are dendritic cells (DCs). Expression of VDR by purified tissue DCs was first reported in 198715. Subsequent studies using populations of DCs isolated from skin (Langerhans cells) provided evidence that 1,25(OH)2D3 could act to attenuate antigen presentation 20. However, it was not until the later advent of in vitro monocyte-derived DC models that the effects of vitamin D metabolites on antigen presentation were fully elucidated. In 2000 parallel studies by the Adorini and Kumar groups showed that 1,25(OH)2D376 and its synthetic analogs 34 inhibited the maturation of monocyte-derived DCs, thereby suppressing their capacity to present antigen to T-cells. Based on these observations, it was proposed that vitamin D could act to promote tolerance and this was endorsed by studies of pancreatic islet transplantation in which lower rejection rates were observed in 1,25(OH)2D3-treated mice 32. Crucially this response to 1,25(OH)2D3 appeared to be due to decreased DC maturation and concomitant enhancement of suppressor or regulatory T-cells (Treg) 32. Further studies have underlined the importance of Treg generation 68 as part of the interaction between vitamin D and the immune system and this is discussed in greater detail in later sections of this review.

 

Figure 1
Effects of vitamin D on innate and adaptive immunity

Although regulation of DC maturation represents at potential target for 1,25(OH)2D3 and its synthetic analogs as treatment for autoimmune disease and host-graft rejection, another perspective was provided by the observation that DCs express 1α-hydroxylase in a similar fashion to macrophages 25,40. Data from monocyte-derived DCs showed that 1α-hydroxylase expression and activity increases as DCs differentiate towards an a mature phenotype 40. Functional analyses showed that treatment with 25OHD3 suppresses DC maturation and inhibits T-cell proliferation, confirming the existence of an intracrine pathway for vitamin D similar to that observed for macrophages 40. Interestingly, mature DCs showed lower levels of VDR than immature DCs or monocytes 40. This reciprocal organization of 1α-hydroxylase and VDR expression may be advantageous in that mature antigen-presenting DCs may be relatively insensitive to 1,25(OH)2D3, thereby allowing induction of an initial T-cell response. However, the high levels of 1,25(OH)2D3 being synthesized by these cells will be able to act on VDR-expressing immature DCs and thus prevent their further development 41. In this way, paracrine action of locally produced 1,25(OH)2D3 will allow initial presentation of antigen to T-cells whilst preventing continued maturation of DCs and over-stimulation of T-cells.

Although DCs are heterogeneous in terms of their location, phenotype and function, they are broadly divided into two groups based on their origin. Myeloid (mDCs) and plasmacytoid (pDCs) express different types of cytokines and chemokines and appear to exert complementary effects on T-cell responses, with mDCs being the most effective APCs 57 and pDCs being more closely associated with immune tolerance 91. It is therefore interesting to note that 1,25(OH)2D3 preferentially regulates mDCs, suggesting that the key effect of vitamin D in this instance is to suppress activation of naïve T-cells. Although in this study pDCs showed no apparent immune response to 1,25(OH)2D3, this does not preclude a role for vitamin D in the regulation of tolerogenic responses. One possibility is that local, intracrine, synthesis of 1,25(OH)2D3 will be more effective in achieving these responses. Alternatively, 1,25(OH)2D3 synthesized by pDCs may regulate tolerance through paracrine effects on VDR-expressing T-cells. This is discussed in further detail in the following section.

Vitamin D and adaptive immunity
Vitamin D and T-cell function

Resting T-cells express almost undetectable levels of VDR, but levels of the receptor increase as T-cells proliferate following antigenic activation 44,66,78. As a consequence, initial studies of the effects of vitamin D on T-cells focused on the ability of 1,25(OH)2D3 to suppress T-cell proliferation 44,66,78. However, the recognition that CD4+ effector T-cells were capable of considerable phenotypic plasticity, suggested that vitamin D might also influence the phenotype of T-cells. Lemire and colleagues first reported that 1,25(OH)2D3 preferentially inhibited T-helper 1 (Th1) cells which are a subset of CD4+ effector T-cells closely associated with cellular, rather than humoral, immune responses 52. Subsequent studies confirmed this observation and demonstrated that the cytokine profile of 1,25(OH)2D3-treated human T-cells was consistent with Th2 cells, a subset of CD4+ T-cells associated with humoral (antibody)-mediated immunity 14,70. The conclusion from these observations was that vitamin D promotes a T-cell shift from Th1 to Th2 and thus might help to limit the potential tissue damage associated with Th1 cellular immune responses. However, the validity of this generalization was called into question by studies using mouse T-cells in which 1,25(OH)2D3 was shown to inhibit cytokines associated with both Th1 (IFNγ) and Th2 (interleukin-4, IL-4). Subsequent analysis of immune cells from the VDR gene knockout mouse added further confusion by showing that these animals had reduced (rather than the predicted elevated) levels of Th1 cells 69. Thus, whilst in vitro vitamin D appears to broadly support a shift from Th1 to Th2 in CD4+ cells, it seems likely that in vivo its effects on T-cells are more complex.

The T-cell repertoire has continued to expand with the characterization of another effector T-cell lineage distinct from Th1 or Th2 cells, termed Th17 cells because of their capacity to synthesize interleukin-17 (IL-17) 36,101. Th17 cells play an essential role in combating certain pathogens but they have also been linked to tissue damage and inflammation 12,48. The precise role of vitamin D as a regulator of Th17 cells has yet to be fully elucidated but it is interesting to note that studies of animal models of the gastrointestinal inflammatory disease colitis have shown that treatment with 1,25(OH)2D3 reduces expression of IL-1721, whilst loss of 1,25(OH)2D3 as a result of CYP27b1 gene ablation leads to elevated levels of this cytokine 55. Thus, it possible that vitamin D exerts some of its effects on inflammation and autoimmune disease through the regulation of Th17 cells.

A fourth group of CD4+ T-cells, exert suppressor rather than effector functions and are known as regulatory T-cells or Tregs. In view of its early recognition as a suppressor of T-cell proliferation, it was anticipated that vitamin D would have effects on Tregs, and indeed in 2002 O’Garra and colleagues demonstrated that 1,25(OH)2D3, in conjunction with glucocorticoids, potently stimulated the generation of interleukin-10 (IL-10)-producing CD4+/CD25+ Tregs 10. Subsequent reports indicated that 1,25(OH)2D3 alone can induce Tregs 31, and it appears that preferential differentiation of Tregs is a pivotal mechanism linking vitamin D and adaptive immunity, with potential beneficial effects for autoimmune disease and host-graft rejection 33,62,89. This immunosuppressive mechanism is likely to be mediated by the induction of tolerogenic DCs as described in the previous section of the review 7,22,32, but direct effects on T-cells may also be important 95. In this latter study, it was notable that 1,25(OH)2D3 increased both IL-10-secretion and TLR9 expression by Tregs, suggesting a novel link between innate and adaptive immune responses 95.

Relative to the wealth of literature on CD4+ effector cells, our understanding of the effects of vitamin D on CD8+ suppressor T-cells remains somewhat limited. In contrast to CD4+ cells, CD8+ show poor antiproliferative response to 1,25(OH)2D378,98,99. However, VDR expression appears to be abundant in CD8+ cells suggesting that they are still potential targets for 1,25(OH)2D3. Indeed subsequent reports have shown that 1,25(OH)2D3 actively regulates cytokine production by CD8+ cells 103, and can also regulate the proliferation of CD8+ cells following specific immune stimuli 43. Despite this, 1,25(OH)2D3 does not appear to have a significant impact on animal disease models such as experimental autoimmune encephalomyelitis where CD8+ cells have been implicated 65.

Although many of the studies linking 1,25(OH)2D3 with adaptive immunity have focused on changes in T-cell proliferation and phenotype, it is important to recognize that other facets of T-cell function may also be affected by the hormone. In particular recent studies have shown that vitamin D can exert powerful effects on the homing of T-cells to specific tissues. Initial studies suggested that 1,25(OH)2D3 acts to inhibit migration of T-cells to lymph nodes 94. However, more recent reports have demonstrated an active role for vitamin D in promoting homing of T-cells to the skin via upregulation of chemokine receptor 10 (CCR10), the ligand for which, CCL27, is expressed by epidermal keratinocytes 87. Notably this T-cell homing response was induced by 25OHD3 as well as 1,25(OH)2D3 and the author suggested that both DCs and T-cells were possible sources of the local 1α-hydroxylase activity 87. In contrast to its positive effect on epidermal T-cell homing, vitamin D appears to exert a negative effect on chemokines and chemokine receptors associated with the GI tract 87. However, it seems likely that this is will be highly T-cell selective as newer studies using the VDR gene knockout mouse have demonstrated aberrant GI migration of a subset of CD8+ cells, and this effects appears to be closely linked to the increased risk of colitis in VDR knockout mice 105.

Vitamin D and B-cell function

Like T-cells, active but not inactive B-cells express the VDR 79. Consequently, initial studies indicated that 1,25(OH)2D3 could directly regulate B-cell proliferation 86 and immunoglobulin (Ig) production 79. Subsequent work contradicted this, suggesting instead that the ability of 1,25(OH)2D3 to suppress proliferation and immunoglobulin (Ig) production was due to indirect effects mediated via helper T-cells 51. However, more recent reports have demonstrated that 1,25(OH)2D3 does indeed exert direct effects on B cell homeostasis 17. In addition to confirming direct VDR-mediated effects on B cell proliferation and Ig production, this study also highlighted the ability of 1,25(OH)2D3 to inhibit the differentiation of plasma cells and class switched memory cells, suggesting a potential role for vitamin D in B cell-related disorders such as systemic lupus erythamtosus. Notably, expression of CYP27b1 was also detected in B-cells, indicating that B-cells may be capable of autocrine/intracrine responses to vitamin D 17. Indeed, this may be common to lymphocytes in general as CYP27b1 expression has also been detected in T-cells 87.

Vitamin D, the immune system and human health

For many years vitamin D status was defined simply by whether or not the patient in question exhibited symptoms of the bone disease rickets (osteomalacia in adults). However, an entirely new perspective on vitamin D status has arisen from the observation that serum levels of the main circulating form of vitamin D (25OHD3) as high as 75 nM correlate inversely with parathyroid hormone 16. This, has prompted the introduction of a new term – vitamin D ‘insufficiency’ – defined by serum levels of 25OHD3 that are sub-optimal (< 75 nM) but not necessarily rachitic (< 20 nM) 42. Unlike serum concentrations of 1,25(OH)2D3, which are primarily defined by the endocrine regulators of the vitamin D-activating enzyme, 1α-hydroxylase, circulating levels of 25OHD3 are a direct reflection of vitamin D status, which for any given individual will depend on access to vitamin D either through exposure to sunlight or through dietary intake. The net effect of this is that vitamin D status can vary significantly in populations depending on geographical, social or economic factors. As a result of these new parameters for vitamin D status, a consensus statement from the 13th Workshop on Vitamin D concluded that vitamin D insufficiency was a worldwide epidemic. Moreover, recent studies have shown that in the last ten years alone, serum vitamin D levels have on average fallen by 20% 28. The key question now being considered is what is the physiological and clinical impact of global vitamin D insufficiency beyond classical bone diseases such as rickets? Epidemiological studies have highlighted possible links between vitamin D insufficiency and a wide range of human diseases 42. The final section of the review will describe four of the key clinical problems which have been linked to the immunomodulatory properties of vitamin D.

Vitamin D and tuberculosis

The observation that vitamin D acts to promote innate immune responses to TLR-activation by M. tb 56, has provided a new perspective on observations made many decades ago concerning the beneficial effects of UV light exposure on the disease TB. As a consequence this has become the most well studied facet of the interaction between vitamin D and innate immunity 60. Initial studies to assess the effects of 25OHD status on ex vivo macrophage function have shown that supplementation with a single oral dose of 2.5 mg vitamin D enhances the ability of recipient macrophages to combat BCG infection in vitro 61. The potential benefits of vitamin D as treatment for tuberculosis (TB) have been further endorsed by a study which showed that adjunct vitamin D supplementation (0.25 mg vitamin D/day) of TB patients receiving conventional therapy for the disease reduced the time for sputum smear conversion from acid fast bacteria (AFB) positive to AFB-negative status 67. A recent double-blind randomized placebo-controlled trial showed that vitamin D supplementation had no effect on clinical outcomes or mortality amongst TB patients, although it should be emphasized that none of the supplemented patients in this study showed a significant rise in serum vitamin D levels 102.

Vitamin D and multiple sclerosis

Several epidemiology studies have reported association between vitamin D insufficiency and the incidence and/or severity of the autoimmune disease multiple sclerosis (MS) (reviewed in 80. These observations have been supported by analysis of animal models such as the experimental autoimmune encephalomyelitis (EAE) mouse, which shows increased disease severity under dietary vitamin D restriction 88. Conversely administration of 1,25(OH)2D3 to EAE mice confers disease protection through effects on cytokine synthesis and apoptosis of inflammatory cells 75,90. Some effects of 1,25(OH)2D3 on EAE appear to be dependent on IL-10 activity 89.

Vitamin D and type 1 diabetes

In common with MS, published reports suggest that there is a link between vitamin D deficiency and another autoimmune disease, type 1 diabetes (reviewed in 63). Low circulating levels of 25OHD3 have been reported in adolescents at the time of diagnosis of type 1 diabetes 53, and other data have documented the beneficial effects of vitamin D supplementation in protecting against type 1 diabetes 37. Another strand of evidence linking vitamin D with type 1 diabetes stems from the extensive genetic analyses that have explored the physiological impact of inherited variations in the genes for various components of the vitamin D metabolic and signaling system. Previous studies have indicated that some VDR gene haplotypes confer protection against diabetes 81 and more recently this has been expanded to show that genetic variants of the CYP27b1 gene also affect susceptibility to type 1 diabetes 8. Finally, in a similar fashion to animal model studies for MS, in vivo use of the non-obese diabetic (NOD) mouse as a model for type 1 diabetes has shown increased disease severity under conditions of dietary vitamin D restriction 29.

Vitamin D and Crohn’s disease

Several strands of evidence have linked vitamin D to the dysregulated immune responses observed with inflammatory bowel diseases such as Crohn’s disease. Firstly, epidemiology suggests that patients with Crohn’s disease have decreased serum levels of 25OHD373,74,96. Secondly, studies in vivo using various animal models indicate that 1,25(OH)2D3 plays a crucial role in the pathophysiology of experimentally-induced forms of inflammatory bowel disease 26,27,47,55. Finally, expression of 1α-hydroxylase has been detected in the human colon 106, with the vitamin D-activating enzyme being upregulated in disease-affected tissue from patients with Crohn’s disease 3. In the case of the latter, dysregulated colonic expression of 1α-hydroxylase was associated with increased circulating levels of 1,25(OH)2D3 indicating that, as with sarcoidosis, localized synthesis of this vitamin D metabolite can spill-over into the general circulation under conditions of persistent disease 3. Intriguingly, current studies have implicated aberrant innate immune handling of enteric microbiota as an initiator of the adaptive immune damage associated with Crohn’s disease 71. It is thus tempting to speculate that effects of vitamin D on this disease may involve both the activation of innate immunity, together with the suppression of adaptive immunity and associated inflammation.

Conclusions

It is almost thirty years since an interaction between vitamin D and the immune system was first documented. Although this was initially proposed as a non-classical effect of vitamin D associated with granulomatous diseases, our current view is now considerably changed. Recent studies have demonstrated a potential physiological role for vitamin D in regulating normal innate and adaptive immunity. Future studies will now need to focus on the clinical implications of vitamin D-mediated immunity and, in particular, the possible beneficial effects of supplementary vitamin D with respect to infectious and autoimmune diseases.

Acknowledgments

This work was supported by NIH grant RO1AR050626 to M.H.
Footnotes

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80. Raghuwanshi A, Joshi SS, Christakos S. Vitamin D and multiple sclerosis. J Cell Biochem. 2008;105:338. [PMC free article] [PubMed]

81. Ramos-Lopez E, Jansen T, Ivaskevicius V, et al. Protection from type 1 diabetes by vitamin D receptor haplotypes. Ann N Y Acad Sci. 2006;1079:327. [PubMed]

82. Ren S, Nguyen L, Wu S, et al. Alternative splicing of vitamin D-24-hydroxylase: a novel mechanism for the regulation of extrarenal 1,25-dihydroxyvitamin D synthesis. J Biol Chem. 2005;280:20604. [PubMed]

83. Sadeghi K, Wessner B, Laggner U, et al. Vitamin D3 down-regulates monocyte TLR expression and triggers hyporesponsiveness to pathogen-associated molecular patterns. Eur J Immunol. 2006;36:361. [PubMed]

84. Schauber J, Dorschner RA, Coda AB, et al. Injury enhances TLR2 function and antimicrobial peptide expression through a vitamin D-dependent mechanism. J Clin Invest. 2007;117:803. [PMC free article] [PubMed]

85. Schauber J, Dorschner RA, Yamasaki K, et al. Control of the innate epithelial antimicrobial response is cell-type specific and dependent on relevant microenvironmental stimuli. Immunology. 2006;118:509. [PMC free article] [PubMed]

86. Shiozawa K, Shiozawa S, Shimizu S, et al. 1 alpha,25-dihydroxyvitamin D3 inhibits pokeweed mitogen-stimulated human B-cell activation: an analysis using serum-free culture conditions. Immunology. 1985;56:161. [PMC free article] [PubMed]

87. Sigmundsdottir H, Pan J, Debes GF, et al. DCs metabolize sunlight-induced vitamin D3 to ‘program’ T cell attraction to the epidermal chemokine CCL27. Nat Immunol. 2007;8:285. [PubMed]

88. Spach KM, Hayes CE. Vitamin D3 confers protection from autoimmune encephalomyelitis only in female mice. J Immunol. 2005;175:4119. [PubMed]

89. Spach KM, Nashold FE, Dittel BN, et al. IL-10 signaling is essential for 1,25-dihydroxyvitamin D3-mediated inhibition of experimental autoimmune encephalomyelitis. J Immunol. 2006;177:6030. [PubMed]

90. Spach KM, Pedersen LB, Nashold FE, et al. Gene expression analysis suggests that 1,25-dihydroxyvitamin D3 reverses experimental autoimmune encephalomyelitis by stimulating inflammatory cell apoptosis. Physiol Genomics. 2004;18:141. [PubMed]

91. Steinman RM, Hawiger D, Nussenzweig MC. Tolerogenic dendritic cells. Annu Rev Immunol. 2003;21:685. [PubMed]

92. Stoffels K, Overbergh L, Giulietti A, et al. Immune regulation of 25-hydroxyvitamin-d(3)-1alpha-hydroxylase in human monocytes. J Bone Miner Res. 2006;21:37. [PubMed]

93. Tanaka H, Abe E, Miyaura C, et al. 1 alpha,25-dihydroxyvitamin D3 induces differentiation of human promyelocytic leukemia cells (HL-60) into monocyte-macrophages, but not into granulocytes. Biochem Biophys Res Commun. 1983;117:86. [PubMed]

94. Topilski I, Flaishon L, Naveh Y, et al. The anti-inflammatory effects of 1,25-dihydroxyvitamin D3 on Th2 cells in vivo are due in part to the control of integrin-mediated T lymphocyte homing. Eur J Immunol. 2004;34:1068. [PubMed]

95. Urry Z, Xystrakis E, Richards DF, et al. Ligation of TLR9 induced on human IL-10-secreting Tregs by 1alpha,25-dihydroxyvitamin D3 abrogates regulatory function. J Clin Invest. 2009;119:387. [PMC free article] [PubMed]

96. Vagianos K, Bector S, McConnell J, et al. Nutrition assessment of patients with inflammatory bowel disease. JPEN J Parenter Enteral Nutr. 2007;31:311. [PubMed]

97. Van Etten E, Decallonne B, Verlinden L, et al. Analogs of 1alpha,25-dihydroxyvitamin D3 as pluripotent immunomodulators. J Cell Biochem. 2003;88:223. [PubMed]

98. Vanham G, Ceuppens JL, Bouillon R. T lymphocytes and their CD4 subset are direct targets for the inhibitory effect of calcitriol. Cell Immunol. 1989;124:320. [PubMed]

99. Veldman CM, Cantorna MT, DeLuca HF. Expression of 1,25-dihydroxyvitamin D(3) receptor in the immune system. Arch Biochem Biophys. 2000;374:334. [PubMed]

100. Wang TT, Nestel FP, Bourdeau V, et al. Cutting edge: 1,25-dihydroxyvitamin D3 is a direct inducer of antimicrobial peptide gene expression. J Immunol. 2004;173:2909. [PubMed]

101. Weaver CT, Hatton RD, Mangan PR, et al. IL-17 family cytokines and the expanding diversity of effector T cell lineages. Annu Rev Immunol. 2007;25:821. [PubMed]

102. Wejse C, Gomes VF, Rabna P, et al. Vitamin D as supplementary treatment for tuberculosis: a double-blind, randomized, placebo-controlled trial. Am J Respir Crit Care Med. 2009;179:843. [PubMed]

103. Willheim M, Thien R, Schrattbauer K, et al. Regulatory effects of 1alpha,25-dihydroxyvitamin D3 on the cytokine production of human peripheral blood lymphocytes. J Clin Endocrinol Metab. 1999;84:3739. [PubMed]

104. Yim S, Dhawan P, Ragunath C, et al. Induction of cathelicidin in normal and CF bronchial epithelial cells by 1,25-dihydroxyvitamin D(3) J Cyst Fibros. 2007;6:403. [PMC free article] [PubMed]

105. Yu S, Bruce D, Froicu M, et al. Failure of T cell homing, reduced CD4/CD8alphaalpha intraepithelial lymphocytes, and inflammation in the gut of vitamin D receptor KO mice. Proc Natl Acad Sci U S A. 2008;105:20834. [PMC free article] [PubMed]

106. Zehnder D, Bland R, Williams MC, et al. Extrarenal expression of 25-hydroxyvitamin d(3)-1 alpha-hydroxylase. J Clin Endocrinol Metab. 2001;86:888. [PubMed]
________________________________________ PubMed articles by these authors
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• Therapeutic potential of vitamin D for multiple sclerosis.Therapeutic potential of vitamin D for multiple sclerosis.
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• 1,25-dihydroxyvitamin-D-receptor in breast cancer cells.
Lancet. 1979 Dec 22-29; 2(8156-8157):1335-6.
[Lancet. 1979]
• 1,25-dihydroxyvitamin D3 receptors in cancer.
Lancet. 1980 Apr 12; 1(8172):828.
[Lancet. 1980]
• Differentiation of mouse myeloid leukemia cells induced by 1 alpha,25-dihydroxyvitamin D3.
Proc Natl Acad Sci U S A. 1981 Aug; 78(8):4990-4.
[Proc Natl Acad Sci U S A. 1981]
• 1,25-dihydroxyvitamin D3 and malignant melanoma: the presence of receptors and inhibition of cell growth in culture.
Endocrinology. 1981 Mar; 108(3):1083-6.
[Endocrinology. 1981]
• 1 alpha,25-dihydroxyvitamin D3 promotes fusion of mouse alveolar macrophages both by a direct mechanism and by a spleen cell-mediated indirect mechanism.
Proc Natl Acad Sci U S A. 1983 Sep; 80(18):5583-7.
[Proc Natl Acad Sci U S A. 1983]
See more articles cited in this paragraph
• Extra-renal 25-hydroxyvitamin D3-1alpha-hydroxylase in human health and disease.
J Steroid Biochem Mol Biol. 2007 Mar; 103(3-5):316-21.
[J Steroid Biochem Mol Biol. 2007]
• ReviewVitamin D and its analogs as regulators of immune activation and antigen presentation.
Annu Rev Nutr. 2003; 23():117-45.
[Annu Rev Nutr. 2003]
• ReviewAnalogs of 1alpha,25-dihydroxyvitamin D3 as pluripotent immunomodulators.
J Cell Biochem. 2003 Feb 1; 88(2):223-6.
[J Cell Biochem. 2003]

• Differentiation of mouse myeloid leukemia cells induced by 1 alpha,25-dihydroxyvitamin D3.
Proc Natl Acad Sci U S A. 1981 Aug; 78(8):4990-4.
[Proc Natl Acad Sci U S A. 1981]
• 1 alpha,25-dihydroxyvitamin D3 promotes fusion of mouse alveolar macrophages both by a direct mechanism and by a spleen cell-mediated indirect mechanism.
Proc Natl Acad Sci U S A. 1983 Sep; 80(18):5583-7.
[Proc Natl Acad Sci U S A. 1983]
• Induction of macrophage differentiation of human normal and leukemic myeloid stem cells by 1,25-dihydroxyvitamin D3 and its fluorinated analogues.
Cancer Res. 1984 Dec; 44(12 Pt 1):5624-8.
[Cancer Res. 1984]
• 1 alpha,25-dihydroxyvitamin D3 induces differentiation of human promyelocytic leukemia cells (HL-60) into monocyte-macrophages, but not into granulocytes.
Biochem Biophys Res Commun. 1983 Nov 30; 117(1):86-92.
[Biochem Biophys Res Commun. 1983]
• 1,25-dihydroxyvitamin D3 production and vitamin D3 receptor expression are developmentally regulated during differentiation of human monocytes into macrophages.
Blood. 1993 Aug 15; 82(4):1300-7.
[Blood. 1993]
See more articles cited in this paragraph
• Toll-like receptor triggering of a vitamin D-mediated human antimicrobial response.
Science. 2006 Mar 24; 311(5768):1770-3.
[Science. 2006]
• Vitamin d-directed rheostatic regulation of monocyte antibacterial responses.
J Immunol. 2009 Apr 1; 182(7):4289-95.
[J Immunol. 2009]
• Human cathelicidin antimicrobial peptide (CAMP) gene is a direct target of the vitamin D receptor and is strongly up-regulated in myeloid cells by 1,25-dihydroxyvitamin D3.
FASEB J. 2005 Jul; 19(9):1067-77.
[FASEB J. 2005]
• Cutting edge: 1,25-dihydroxyvitamin D3 is a direct inducer of antimicrobial peptide gene expression.
J Immunol. 2004 Sep 1; 173(5):2909-12.
[J Immunol. 2004]

• Immune regulation of 25-hydroxyvitamin-D3-1alpha-hydroxylase in human monocytes.
J Bone Miner Res. 2006 Jan; 21(1):37-47.
[J Bone Miner Res. 2006]
• IL-15 links TLR2/1-induced macrophage differentiation to the vitamin D-dependent antimicrobial pathway.
J Immunol. 2008 Nov 15; 181(10):7115-20.
[J Immunol. 2008]
• IL-17A enhances vitamin D3-induced expression of cathelicidin antimicrobial peptide in human keratinocytes.
J Immunol. 2008 Dec 15; 181(12):8504-12.
[J Immunol. 2008]
• Toll-like receptor triggering of a vitamin D-mediated human antimicrobial response.
Science. 2006 Mar 24; 311(5768):1770-3.
[Science. 2006]
• Alternative splicing of vitamin D-24-hydroxylase: a novel mechanism for the regulation of extrarenal 1,25-dihydroxyvitamin D synthesis.
J Biol Chem. 2005 May 27; 280(21):20604-11.
[J Biol Chem. 2005]

• Injury enhances TLR2 function and antimicrobial peptide expression through a vitamin D-dependent mechanism.
J Clin Invest. 2007 Mar; 117(3):803-11.
[J Clin Invest. 2007]
• Control of the innate epithelial antimicrobial response is cell-type specific and dependent on relevant microenvironmental stimuli.
Immunology. 2006 Aug; 118(4):509-19.
[Immunology. 2006]
• Cutting edge: 1,25-dihydroxyvitamin D3 is a direct inducer of antimicrobial peptide gene expression.
J Immunol. 2004 Sep 1; 173(5):2909-12.
[J Immunol. 2004]
• Induction of cathelicidin in normal and CF bronchial epithelial cells by 1,25-dihydroxyvitamin D(3).
J Cyst Fibros. 2007 Nov 30; 6(6):403-10.
[J Cyst Fibros. 2007]
• Human cathelicidin antimicrobial peptide (CAMP) gene is a direct target of the vitamin D receptor and is strongly up-regulated in myeloid cells by 1,25-dihydroxyvitamin D3.
FASEB J. 2005 Jul; 19(9):1067-77.
[FASEB J. 2005]
See more articles cited in this paragraph
• Vitamin D receptor as an intestinal bile acid sensor.
Science. 2002 May 17; 296(5571):1313-6.
[Science. 2002]
• Bile salts control the antimicrobial peptide cathelicidin through nuclear receptors in the human biliary epithelium.
Gastroenterology. 2009 Apr; 136(4):1435-43.
[Gastroenterology. 2009]

• Alternative splicing of vitamin D-24-hydroxylase: a novel mechanism for the regulation of extrarenal 1,25-dihydroxyvitamin D synthesis.
J Biol Chem. 2005 May 27; 280(21):20604-11.
[J Biol Chem. 2005]
• Vitamin D3 down-regulates monocyte TLR expression and triggers hyporesponsiveness to pathogen-associated molecular patterns.
Eur J Immunol. 2006 Feb; 36(2):361-70.
[Eur J Immunol. 2006]

• Dendritic cells from human tissues express receptors for the immunoregulatory vitamin D3 metabolite, dihydroxycholecalciferol.
Immunology. 1987 Aug; 61(4):457-61.
[Immunology. 1987]
• 1 Alpha,25-dihydroxyvitamin D3 inhibits differentiation, maturation, activation, and survival of dendritic cells leading to impaired alloreactive T cell activation.
J Immunol. 2000 Mar 1; 164(5):2405-11.
[J Immunol. 2000]
• Potent inhibition of dendritic cell differentiation and maturation by vitamin D analogs.
Biochem Biophys Res Commun. 2000 Apr 21; 270(3):701-8.
[Biochem Biophys Res Commun. 2000]
• Regulatory T cells induced by 1 alpha,25-dihydroxyvitamin D3 and mycophenolate mofetil treatment mediate transplantation tolerance.
J Immunol. 2001 Aug 15; 167(4):1945-53.
[J Immunol. 2001]
• ReviewIn vitro generation of IL-10-producing regulatory CD4+ T cells is induced by immunosuppressive drugs and inhibited by Th1- and Th2-inducing cytokines.
Immunol Lett. 2003 Jan 22; 85(2):135-9.
[Immunol Lett. 2003]

• Regulation of 25-hydroxyvitamin D3-1 alpha-hydroxylase and production of 1 alpha,25-dihydroxyvitamin D3 by human dendritic cells.
Blood. 2003 Nov 1; 102(9):3314-6.
[Blood. 2003]
• Differential regulation of vitamin D receptor and its ligand in human monocyte-derived dendritic cells.
J Immunol. 2003 Jun 1; 170(11):5382-90.
[J Immunol. 2003]
• ReviewVitamin D and barrier function: a novel role for extra-renal 1 alpha-hydroxylase.
Mol Cell Endocrinol. 2004 Feb 27; 215(1-2):31-8.
[Mol Cell Endocrinol. 2004]

• ReviewIPC: professional type 1 interferon-producing cells and plasmacytoid dendritic cell precursors.
Annu Rev Immunol. 2005; 23():275-306.
[Annu Rev Immunol. 2005]
• ReviewTolerogenic dendritic cells.
Annu Rev Immunol. 2003; 21():685-711.
[Annu Rev Immunol. 2003]

• 1,25(OH)2D3 regulates c-myc mRNA levels in tonsillar T lymphocytes.
Immunology. 1991 Dec; 74(4):589-93.
[Immunology. 1991]
• Regulation of human tonsillar T-cell proliferation by the active metabolite of vitamin D3.
Immunology. 1986 Dec; 59(4):479-84.
[Immunology. 1986]
• 1 Alpha,25-dihydroxyvitamin D3 receptor distribution and effects in subpopulations of normal human T lymphocytes.
J Clin Endocrinol Metab. 1989 Apr; 68(4):774-9.
[J Clin Endocrinol Metab. 1989]
• ReviewImmunosuppressive actions of 1,25-dihydroxyvitamin D3: preferential inhibition of Th1 functions.
J Nutr. 1995 Jun; 125(6 Suppl):1704S-1708S.
[J Nutr. 1995]
• 1alpha,25-Dihydroxyvitamin d3 has a direct effect on naive CD4(+) T cells to enhance the development of Th2 cells.
J Immunol. 2001 Nov 1; 167(9):4974-80.
[J Immunol. 2001]
See more articles cited in this paragraph
• ReviewExpanding the effector CD4 T-cell repertoire: the Th17 lineage.
Curr Opin Immunol. 2006 Jun; 18(3):349-56.
[Curr Opin Immunol. 2006]
• ReviewIL-17 family cytokines and the expanding diversity of effector T cell lineages.
Annu Rev Immunol. 2007; 25():821-52.
[Annu Rev Immunol. 2007]
• ReviewTh17: the third member of the effector T cell trilogy.
Curr Opin Immunol. 2007 Dec; 19(6):652-7.
[Curr Opin Immunol. 2007]
• ReviewTh17 cells: effector T cells with inflammatory properties.
Semin Immunol. 2007 Dec; 19(6):362-71.
[Semin Immunol. 2007]
• Altered endocrine and autocrine metabolism of vitamin D in a mouse model of gastrointestinal inflammation.
Endocrinology. 2008 Oct; 149(10):4799-808.
[Endocrinology. 2008]

• In vitro generation of interleukin 10-producing regulatory CD4(+) T cells is induced by immunosuppressive drugs and inhibited by T helper type 1 (Th1)- and Th2-inducing cytokines.
J Exp Med. 2002 Mar 4; 195(5):603-16.
[J Exp Med. 2002]
• Topically applied 1,25-dihydroxyvitamin D3 enhances the suppressive activity of CD4+CD25+ cells in the draining lymph nodes.
J Immunol. 2007 Nov 1; 179(9):6273-83.
[J Immunol. 2007]
• A 1alpha,25-dihydroxyvitamin D(3) analog enhances regulatory T-cells and arrests autoimmune diabetes in NOD mice.
Diabetes. 2002 May; 51(5):1367-74.
[Diabetes. 2002]
• ReviewVitamin D and type 1 diabetes mellitus: state of the art.
Trends Endocrinol Metab. 2005 Aug; 16(6):261-6.
[Trends Endocrinol Metab. 2005]
• IL-10 signaling is essential for 1,25-dihydroxyvitamin D3-mediated inhibition of experimental autoimmune encephalomyelitis.
J Immunol. 2006 Nov 1; 177(9):6030-7.
[J Immunol. 2006]
See more articles cited in this paragraph
• 1 Alpha,25-dihydroxyvitamin D3 receptor distribution and effects in subpopulations of normal human T lymphocytes.
J Clin Endocrinol Metab. 1989 Apr; 68(4):774-9.
[J Clin Endocrinol Metab. 1989]
• T lymphocytes and their CD4 subset are direct targets for the inhibitory effect of calcitriol.
Cell Immunol. 1989 Dec; 124(2):320-33.
[Cell Immunol. 1989]
• Expression of 1,25-dihydroxyvitamin D(3) receptor in the immune system.
Arch Biochem Biophys. 2000 Feb 15; 374(2):334-8.
[Arch Biochem Biophys. 2000]
• Regulatory effects of 1alpha,25-dihydroxyvitamin D3 on the cytokine production of human peripheral blood lymphocytes.
J Clin Endocrinol Metab. 1999 Oct; 84(10):3739-44.
[J Clin Endocrinol Metab. 1999]
• Mechanism in 1,25(OH)2D3-induced suppression of helper/suppressor function of CD4/CD8 cells to immunoglobulin production in B cells.
Cell Immunol. 1990 Apr 15; 127(1):12-25.
[Cell Immunol. 1990]
See more articles cited in this paragraph
• The anti-inflammatory effects of 1,25-dihydroxyvitamin D3 on Th2 cells in vivo are due in part to the control of integrin-mediated T lymphocyte homing.
Eur J Immunol. 2004 Apr; 34(4):1068-76.
[Eur J Immunol. 2004]
• DCs metabolize sunlight-induced vitamin D3 to ‘program’ T cell attraction to the epidermal chemokine CCL27.
Nat Immunol. 2007 Mar; 8(3):285-93.
[Nat Immunol. 2007]
• Failure of T cell homing, reduced CD4/CD8alphaalpha intraepithelial lymphocytes, and inflammation in the gut of vitamin D receptor KO mice.
Proc Natl Acad Sci U S A. 2008 Dec 30; 105(52):20834-9.
[Proc Natl Acad Sci U S A. 2008]

• 1 alpha,25-Dihydroxyvitamin D3-binding macromolecules in human B lymphocytes: effects on immunoglobulin production.
J Immunol. 1986 Apr 15; 136(8):2734-40.
[J Immunol. 1986]
• 1 alpha,25-dihydroxyvitamin D3 inhibits pokeweed mitogen-stimulated human B-cell activation: an analysis using serum-free culture conditions.
Immunology. 1985 Sep; 56(1):161-7.
[Immunology. 1985]
• 1 alpha,25-dihydroxyvitamin D3 suppresses proliferation and immunoglobulin production by normal human peripheral blood mononuclear cells.
J Clin Invest. 1984 Aug; 74(2):657-61.
[J Clin Invest. 1984]
• Modulatory effects of 1,25-dihydroxyvitamin D3 on human B cell differentiation.
J Immunol. 2007 Aug 1; 179(3):1634-47.
[J Immunol. 2007]
• DCs metabolize sunlight-induced vitamin D3 to ‘program’ T cell attraction to the epidermal chemokine CCL27.
Nat Immunol. 2007 Mar; 8(3):285-93.
[Nat Immunol. 2007]

• Prevalence of vitamin D insufficiency in an adult normal population.
Osteoporos Int. 1997; 7(5):439-43.
[Osteoporos Int. 1997]
• ReviewVitamin D deficiency.
N Engl J Med. 2007 Jul 19; 357(3):266-81.
[N Engl J Med. 2007]
• Demographic differences and trends of vitamin D insufficiency in the US population, 1988-2004.
Arch Intern Med. 2009 Mar 23; 169(6):626-32.
[Arch Intern Med. 2009]

• Toll-like receptor triggering of a vitamin D-mediated human antimicrobial response.
Science. 2006 Mar 24; 311(5768):1770-3.
[Science. 2006]
• ReviewVitamin D in the treatment of pulmonary tuberculosis.
J Steroid Biochem Mol Biol. 2007 Mar; 103(3-5):793-8.
[J Steroid Biochem Mol Biol. 2007]
• A single dose of vitamin D enhances immunity to mycobacteria.
Am J Respir Crit Care Med. 2007 Jul 15; 176(2):208-13.
[Am J Respir Crit Care Med. 2007]
• The effect of vitamin D as supplementary treatment in patients with moderately advanced pulmonary tuberculous lesion.
Acta Med Indones. 2006 Jan-Mar; 38(1):3-5.
[Acta Med Indones. 2006]
• Vitamin D as supplementary treatment for tuberculosis: a double-blind, randomized, placebo-controlled trial.
Am J Respir Crit Care Med. 2009 May 1; 179(9):843-50.
[Am J Respir Crit Care Med. 2009]

• ReviewVitamin D and multiple sclerosis.
J Cell Biochem. 2008 Oct 1; 105(2):338-43.
[J Cell Biochem. 2008]
• Vitamin D3 confers protection from autoimmune encephalomyelitis only in female mice.
J Immunol. 2005 Sep 15; 175(6):4119-26.
[J Immunol. 2005]
• 1,25-dihydroxyvitamin D3 reverses experimental autoimmune encephalomyelitis by inhibiting chemokine synthesis and monocyte trafficking.
J Neurosci Res. 2007 Aug 15; 85(11):2480-90.
[J Neurosci Res. 2007]
• Gene expression analysis suggests that 1,25-dihydroxyvitamin D3 reverses experimental autoimmune encephalomyelitis by stimulating inflammatory cell apoptosis.
Physiol Genomics. 2004 Jul 8; 18(2):141-51.
[Physiol Genomics. 2004]
• IL-10 signaling is essential for 1,25-dihydroxyvitamin D3-mediated inhibition of experimental autoimmune encephalomyelitis.
J Immunol. 2006 Nov 1; 177(9):6030-7.
[J Immunol. 2006]

• ReviewVitamin D and diabetes.
Diabetologia. 2005 Jul; 48(7):1247-57.
[Diabetologia. 2005]
• Lower levels of plasma 25-hydroxyvitamin D among young adults at diagnosis of autoimmune type 1 diabetes compared with control subjects: results from the nationwide Diabetes Incidence Study in Sweden (DISS).
Diabetologia. 2006 Dec; 49(12):2847-52.
[Diabetologia. 2006]
• ReviewVitamin D in type 1 diabetes prevention.
J Nutr. 2005 Feb; 135(2):323-5.
[J Nutr. 2005]
• Protection from type 1 diabetes by vitamin D receptor haplotypes.
Ann N Y Acad Sci. 2006 Oct; 1079():327-34.
[Ann N Y Acad Sci. 2006]
• Vitamin D deficiency in early life accelerates Type 1 diabetes in non-obese diabetic mice.
Diabetologia. 2004 Mar; 47(3):451-62.
[Diabetologia. 2004]

• Vitamin D status in children and young adults with inflammatory bowel disease.
Pediatrics. 2006 Nov; 118(5):1950-61.
[Pediatrics. 2006]
• ReviewReport on the vitamin D status of adult and pediatric patients with inflammatory bowel disease and its significance for bone health and disease.
Inflamm Bowel Dis. 2006 Dec; 12(12):1162-74.
[Inflamm Bowel Dis. 2006]
• Nutrition assessment of patients with inflammatory bowel disease.
JPEN J Parenter Enteral Nutr. 2007 Jul-Aug; 31(4):311-9.
[JPEN J Parenter Enteral Nutr. 2007]
• Vitamin D and the vitamin D receptor are critical for control of the innate immune response to colonic injury.
BMC Immunol. 2007 Mar 30; 8():5.
[BMC Immunol. 2007]
• A crucial role for the vitamin D receptor in experimental inflammatory bowel diseases.
Mol Endocrinol. 2003 Dec; 17(12):2386-92.
[Mol Endocrinol. 2003]
See more articles cited in this paragraph
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Cães cobaias: Experimentos com animais revoltam alunos da Universidade Federal de Santa Maria

Cães cobaias: Experimentos com animais revoltam alunos da Universidade Federal de Santa Maria

 

 

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Experimentos com animais revoltam alunos da Universidade Federal de Santa Maria

http://zerohora.clicrbs.com.br/rs/geral/noticia/2012/05/experimentos-com-animais-revoltam-alunos-da-universidade-federal-de-santa-maria-3753990.html

 

Projeto na UFSM removia parte de mandíbulas e maxilares para colocação de placas de titânio

 

Denúncias mostraram cachorros em situação precária, mas doutorando nega maus-tratos aos animais

 

Foto: Jean Pimentel / Agencia RBSÉ

 

 

 

inquestionável o avanço que as pesquisas científicas têm proporcionado no desenvolvimento da medicina humana e veterinária.

 

Mas muitos desses estudos, que utilizam experimentação animal, são polêmicos e deixam indignados quem simpatiza com os bichos.

 

Em Santa Maria, o projeto de um doutorando da Pós-Graduação de Medicina Veterinária da Universidade Federal de Santa Maria (UFSM) revoltou alunos, funcionários e professores do curso.

 

O experimento consistiu em criar e testar uma placa de titânio para recomposição de mandíbulas e maxilares de cães que, por causa de um câncer na boca, tenham passado por cirurgia de remoção de parte ou de toda a mandíbula.

 

O projeto testou o desempenho de próteses humanas e de uma placa específica desenvolvida pelo doutorando com ajuda de engenheiros para a anatomia dos cães.

 

O estudante usou cães cobaias que tiveram parte ou toda a mandíbula retirada para a colocação e teste das placas. O doutorando Cristiano Gomes e o orientador dele, professor Ney Luis Pippi, negaram os maus-tratos.

 

Imagens enviadas ao jornal Diário de Santa Maria – as pessoas que mandaram pediram suas identidades preservadas – mostraram os animais magros, trancados em gaiolas, deitados em meio à própria urina, com pratos de ração virados e vazios, em um ambiente sem condições de higiene.

 

— O problema foi que houve descaso no cuidado com os animais. O Cristiano praticamente não acompanhou o pós-operatório, deixando tudo para estagiários que, muitas vezes, não sabiam nem o que fazer — disse uma estudante, que preferiu não se identificar.

 

Gomes diz que os cães estavam sob os cuidados de 12 pessoas – além dele, quatro doutorandos, três mestrandos e quatro bolsistas da graduação. O estudante teria ficado na cidade até março, acompanhando os animais e, depois, teria mudado para Tubarão (SC), onde passou em um concurso. Segundo ele, depois do seu afastamento, os demais membros do projeto permaneceram cuidando dos bichos.

 

Ainda segundo Gomes, no pós-operatório, os animais teriam ficado cerca de uma semana, recebendo medicação (anti-inflamatórios e antibióticos), diariamente, de manhã, à tarde e à noite. Conforme o doutorando, todos eram alimentados por sonda com ração umedecida e batida no liquidificador.

 

UFSM diz que não sabia dos desdobramentos da pesquisa

 

Tanto a coordenação da pós-graduação em Medicina Veterinária quanto a direção do Hospital Veterinário e a reitoria da UFSM não tinham conhecimento dos desdobramentos da pesquisa sobre câncer de boca em cães.

 

— Fiquei sabendo da história na última sexta-feira. A coordenação (da pós) não tem ingerência sobre os experimentos dos pós-graduandos. A coordenação não tem como sair e inspecionar os cento e poucos alunos que temos — disse a coordenadora da pós-graduação em Medicina Veterinária, professora Sonia Terezinha dos Anjos Lopes.

 

A coordenadora comentou que iria se informar com o doutorando Cristiano Gomes e com seu orientador, Ney Luis Pippi, sobre o ocorrido no projeto.

 

— A área física é a do hospital, mas o hospital não interfere nem nas aulas nem nas pesquisas da pós — disse Luiz Sérgio Segala de Oliveira, diretor do Hospital Veterinário da UFSM.

 

A reitoria disse que só se manifestará sobre o assunto depois do pronunciamento do Comitê de Ética.

 

ZERO HORA

Animais, Santa Maria universidade

Mirella Pacheco

  

Espero uma ação efetiva do Ministerio Publico, CRMS-RS, MEC e da própria UFSM. Saibam que uma cadela prenha foi tb utilizada no “experimento”, conforme a reportagem do Diario de Santa Maria. Leiam a reportagem ATÉ ONDE IR EM NOME DA CIENCIA? Tudo tem limite! Qual a etica deste profissional??

 

11/05/2012 | 11h26

Michele Cunha Lima

 ————

Mais de mil ativistas italianos salvam beagles de experimentos

04/05/2012 | Escrito por

Mais de mil ativistas italianos salvam beagles de experimentos

Tudo pela causa – Um protesto reuniu mais de mil italianos em favor dos beagles que servem de teste para a empresa Green Hill. A multidão conseguiu invadir o criadouro e salvar 40 dos 2.500 cachorros mantidos na instituição.

A ação ocorreu no último sábado (28), após a sociedade italiana conseguir se organizar em favor dos animais indefesos. A Green Hill é um criadouro multinacional de animais para testes em laboratórios ao redor do mundo.

As pessoas saíram às ruas gritando e não pararam quando chegarem ao local onde estavam os cães. Os protestantes simplesmente ignoraram todos os avisos de propriedade privada e invadiram o local. Escalaram os lugares cercados e cortaram arames farpados.

Aos poucos eles conseguiram libertar alguns filhotes, fêmeas grávidas e cães maiores. Entre os manifestantes estavam ativistas e donas de casa que corriam com os animais no colo, enquanto a polícia tentava dispersar a multidão.

Os laboratórios que fazem testes com animais dão preferência aos beagles por eles terem porte pequeno e serem muito mansos, o que facilita o manuseio.

O resultado do protesto foi 40 beagles salvos e 12 pessoas presas. A respeito dessas pessoas que foram detidas a jornalista italiana Gloria Ciabattoni fala que nesta história, como sempre, quem perde são os mais fracos, no caso os cães e os seres humanos.

“Com protestos em dezenas de cidades, os ativistas querem enviar uma mensagem para o governo italiano: dizer não aos experimentos com animais”, afirmou a jornalista em seu blog Quotidiano. Segundo ela, as organizações não querem a empresa em seu país e solicitam a saída do proprietário.

A estimativa é de que mais de 2.500 beagles ainda estejam no criadouro da Green Hill, mas a luta dos ativistas não terminou. Já está marcado para o próximo dia oito de maio o Dia Mundial contra a Green Hill. A data escolhida antecede a análise de emendas na lei italiana sobre experimentos com animais, que ocorrerá na comissão do Senado no dia nove.

Foi criado um site contra a Green Hill, o Fermare Green Hill. O espaço divulga a causa e os italianos se organizam para que o protesto também seja feito em outros países. “Os ativistas terão de enfrentar as embaixadas italianas e consulados, para dar uma mensagem clara ao governo italiano e do Senado”, afirma os organizadores da manifestação, que não possuem qualquer vinculação com partidos políticos. (Do CicloVivo com informações do Vista-se e Quotidiano)

Link para esta matéria: http://ucho.info/?p=55356

 
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O tabagismo pode acelerar a deficiência na esclerose múltipla

O tabagismo pode acelerar a deficiência na esclerose múltipla

Pacientes “MS devem ser aconselhados a parar de fumar, ou pelo menos reduzir, para que possam preservar a função cerebral tanto quanto possível”
15. 15. October 2007 11:49 Outubro 2007 11:49

Persons with multiple sclerosis who smoke risk increasing the amount of brain tissue shrinkage, a consequence of MS, and the subsequent severity of their disease, new research conducted at the Buffalo Neuroimaging Analysis Center (BNAC) at the University at Buffalo has shown. Pessoas com esclerose múltipla que fumam risco de aumentar a quantidade de encolhimento do cérebro do tecido, em consequência da MS, e posteriormente a gravidade de sua doença, novas pesquisas realizadas no Centro de Neuroimagem Búfalo Analysis (BNAC) na universidade no búfalo mostrou.

The results are based on magnetic resonance images (MRIs) of smokers and nonsmokers in 368 MS patients treated in UB’s Jacobs Neurological Institute, the university’s Department of Neurology in its School of Medicine and Biomedical Sciences. Os resultados são baseados em imagens de ressonância magnética (ressonância magnética) dos fumantes e não fumantes em 368 pacientes com EM tratados em Jacobs UB Neurological Institute, departamento de universidade da neurologia na Faculdade de Medicina e Ciências Biomédicas.

Results of the research were presented (Oct. 13, 2007) at the 23rd Congress of the European Committee for the Treatment and Research in Multiple Sclerosis in Prague, Czech Republic. Os resultados da pesquisa foram apresentados (13 de outubro de 2007), no 23 º Congresso do Comitê Europeu para Tratamento e Pesquisa em Esclerose Múltipla, em Praga, República Tcheca.

“Cigarette smoke has many properties that are toxic to the central nervous system, and cigarette smoking has been linked to higher susceptibility and risk of progressive multiple sclerosis ,” said Robert Zivadinov, MD, Ph.D., UB professor of neurology, director of the BNAC and first author on the study. “A fumaça do cigarro tem muitas propriedades que são tóxicos para o sistema nervoso central e tabagismo tem sido associada a maior susceptibilidade e risco de esclerose múltipla progressiva”, disse Robert Zivadinov, MD, Ph.D., professor de neurologia UB, diretor da o BNAC e primeiro autor do estudo.

“Interactions between cigarette smoking and genetic and immunologic factors may point to mechanisms in disease pathogenesis. “Interações entre tabagismo e fatores genéticos e imunológicos podem apontar para os mecanismos na patogênese da doença. No previous studies have investigated differences in MRI characteristics between MS cigarette smokers and MS nonsmokers,” he said. Não há estudos anteriores têm investigado diferenças nas características de MRI entre fumantes e não fumantes MS MS “, disse ele.

The study included patients from the three most common forms of MS: 253 had relapsing-remitting MS — acute attacks with full or partial recovery; nine had primary-progressive MS — steady worsening from onset; and 90 had secondary-progressive MS, characterized by occasional attacks and sustained progression. O estudo incluiu pacientes dos três formas mais comuns de MS: 253 tinha MS reincidente-remitente – ataques agudos com recuperação completa ou parcial; nove o ensino primário-progressiva – piora constante desde o início e tinha 90 Secundariamente Progressiva, caracterizada por ataques ocasionais e progressão sustentada. Another 16 participants had experienced their first MS onset. Outros 16 participantes tinham experimentado o seu primeiro aparecimento MS.

Patients ranged in age from 35-55 years, and had been living with MS for an average of 13 years. Os pacientes variaram na idade de 35-55 anos, e tinha vivido com o MS para uma média de 13 anos. The Expanded Disability Status Scale (EDSS), an average number derived from measures of various functions of the central nervous system based on scales ranging from 0 to 10, was 3.1. O Expanded Disability Status Scale (EDSS), um número médio provenientes de medidas de várias funções do sistema nervoso central, com base em escalas variando de 0 a 10, foi de 3,1. The higher the number, the greater the disability. Quanto maior o número, maior a deficiência.

Within the study cohort, 128 had a history of smoking: 96 were active smokers who had smoked more than 10 cigarettes-per-day in the three months prior to the study start, and 32 were former Dentro do estudo de coorte, 128 tinham história de tabagismo: 96 eram fumantes ativos que fumaram mais de 10 cigarros por dia nos três meses anteriores ao início do estudo, e 32 foram ex –

smokers who had smoked cumulatively for at least 6 months sometime in the past. fumantes que haviam fumado, cumulativamente, para pelo menos 6 meses em algum momento do passado. The remaining 240 participants had no active smoking exposure. Os restantes 240 participantes não tiveram nenhuma exposição tabagismo ativo.

The average smoking duration was 17.6 years and the average number of cigarettes smoked per day was 17. A duração média de fumar foi de 17,6 anos ea média do número de cigarros fumados por dia foi de 17. There were no significant differences between smokers and nonsmokers based on age, disease duration, disease course and total lifetime use of disease-modifying drugs. Não houve diferenças significativas entre fumantes e não fumantes com base na idade, duração da doença, o curso da doença e utilização total da vida de drogas modificadoras da doença.

Analysis and comparison of the MRIs from smokers and nonsmokers showed that the smokers had significantly higher disability scores and lower brain volume than the nonsmokers. Análise e comparação das ressonâncias magnéticas de fumantes e não fumantes mostraram que os fumantes apresentavam escores significativamente mais elevados de deficiência e menor volume cerebral do que os não fumantes. There also was a significant relationship between a higher number of packs-per-day smoked and lower volume of the neocortex, the portion of the cerebral cortex that serves as the center of higher mental functions for humans. Também houve uma relação significativa entre um maior número de pacotes-por-dia fumado e volume mais baixo do neocórtex, a parte do córtex cerebral, que serve como centro de funções mentais superiores dos seres humanos.

There were no significant differences in any of the clinical findings between active and former smokers. Não houve diferença significativa em nenhuma das características clínicas entre fumantes ativos e antigos.

“Smoking appears to influence the severity of MS and to accelerate brain atrophy and the disruption of the blood-brain barrier in MS patients,” said Zivadinov. “Fumar parece influenciar a gravidade de MS e para acelerar a atrofia do cérebro e do rompimento da barreira sangue-cérebro em pacientes com esclerose múltipla”, disse Zivadinov. “MS patients should be counseled to stop smoking, or at least to cut down so they can preserve as much brain function as possible.” Pacientes “MS devem ser aconselhados a parar de fumar, ou pelo menos reduzir, para que possam preservar a função cerebral tanto quanto possível.”

Additional researchers on the study, all from the BNAC or the JNI, were Milena Stosic, MD, Nadir Abdelrahman, MD, Barbara E. Teter, Ph.D., Frederick E. Munschauer, MD, Sara Hussein, Jackie Durfee, Michael G. Dwyer, Jennifer L. Cox, Ph.D., Nima Hani, Fernando Nussenbaum and Bianca Weinstock-Guttman, MD Os investigadores adicionais no estudo, todos do BNAC ou o JNI, foram Milena Stosic, MD, Nadir Abdelrahman, MD, Barbara E. Teter, Ph.D., Frederick E. Munschauer, MD, Sara Hussein, Jackie Durfee, Michael G . Dwyer, Jennifer L. Cox, Ph.D., Nima Hani, Fernando e Bianca Nussenbaum Weinstock-Guttman, MD

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Crescem os casos de esclerose múltipla, dizem especialistas

Crescem os casos de esclerose múltipla, dizem especialistas
15/07/200710h11

Crescem os casos de esclerose múltipla, dizem especialistas

Publicidade
PAULO DE ARAUJO
da Folha de S.Paulo

A esclerose múltipla (EM), doença auto-imune –causada por um ataque do sistema imunológico contra o próprio organismo–, tende a afetar cada vez mais pessoas, segundo especialistas consultados pela Folha. A EM afeta diretamente o sistema nervoso central e pode levar à perda de movimentos.

Uma das hipóteses para esse aumento na prevalência aponta para as condições próprias da vida moderna. A melhoria sanitária nos centros mais desenvolvidos –com a universalização de vacinas, medicamentos e antibióticos– pode provocar uma mudança no padrão imunológico das pessoas, argumenta o neurologista da Faculdade de Ciências Médicas da Santa Casa de São Paulo Charles Tilbery.

“Vivemos em um ambiente mais asséptico, e o organismo fica menos exposto a doenças infecciosas. Quando ativado, o sistema imunológico pode produzir uma hiper-reação”, diz.

De outro lado, a falta de vitamina D também pode estar associada ao aumento da prevalência, explica o professor de neurologia da Unifesp Cícero Galli Coimbra. Segundo ele, os países com radiação solar menos intensa têm uma população mais suscetível à esclerose múltipla. Na Europa e no Canadá, por exemplo, a incidência da doença é mais alta.

“E à medida em que há mais progresso, as pessoas ficam mais confinadas, menos expostas à luz solar [matéria-prima da vitamina D].”

A vitamina D age no sentido de tornar o sistema imunológico mais tolerante. “Os estudos mais promissores sobre o tratamento da esclerose múltipla estão baseados nessa questão.”

Além de haver um aumento na prevalência, a faixa etária dos pacientes com esclerose múltipla tem diminuído nos últimos anos, afirma a neurologista Christiane Pedreira. “Existe um comportamento de antecipação. A cada geração, a doença se manifesta mais cedo. Hoje, é possível observar uma prevalência mais significativa em crianças e adolescentes”.

Estudos insuficientes

Embora um maior número de casos seja observado por alguns neurologistas nos consultórios, não há estudos publicados que demonstrem a evolução da doença. Estima-se que no Brasil a esclerose múltipla afete de 25 mil a 30 mil pessoas. No mundo, são 2 milhões de pessoas afetadas.

Em São Paulo, o último trabalho significativo, realizado em 1997, mostra que a prevalência da doença era de 15 casos por 100 mil habitantes, contra 4,3 casos por 100 mil habitantes registrados em 1992.

Para o chefe do ambulatório de esclerose múltipla do hospital da Universidade de Santo Amaro, Leandro Calia, a falta de dados disponíveis não permite confirmar que esteja realmente havendo um aumento no número de casos. “É uma impressão de consultório, mas as estatísticas são insuficientes”, afirma ele.

De acordo com Maria Fernanda Mendes, da Academia Brasileira de Neurologia, o desenvolvimento do diagnóstico da doença é um fator que deve ser levado em consideração.

“A maior prevalência é uma percepção que os neurologistas começaram a ter. Mas existe também uma melhora na divulgação e no diagnóstico”, afirma.

em

Effect of four monthly oral vitamin D3 (cholecalciferol) supplementation on fractures and mortality in men and women living in the community: randomised double blind controlled trial — Trivedi et al. 326 (7387): 469 — BMJ

BMJ2003;326:469 ( 1 March )

Papers

Effect of four monthly oral vitamin D3 (cholecalciferol) supplementation on fractures and mortality in men and women living in the community: randomised double blind controlled trial

Daksha P Trivedi, research fellowa Richard Doll, emeritus professorb Kay Tee Khaw, professor of clinical gerontologya

a Clinical Gerontology Unit, University of Cambridge School of Clinical Medicine, Addenbrooke’s Hospital, Cambridge CB2 2QQ, b Clinical Trial Service Unit and Epidemiological Studies Unit, University of Oxford

Correspondence to: K T Khaw kk101@medschl.cam.ac.uk // <![CDATA[
var u = “kk101”, d = “medschl.cam.ac.uk”; document.getElementById(“em0”).innerHTML = ‘‘ + u + ‘@’ + d + ”
// ]]>

Objective: To determine the effect of four monthly vitaminD supplementation on the rate of fractures in men and women aged65 years and over living in thecommunity.
Design: Randomised double blind controlled trial of100 000 IU oral vitamin D3 (cholecalciferol) supplementation ormatching placebo every four months over fiveyears.
Setting and participants: 2686 people (2037 men and 649 women) aged65-85 years living in the general community, recruited from theBritish doctors register and a general practice register inSuffolk.
Main outcome measures: Fracture incidence and total mortality bycause.
Results: After five years 268 men and women had incidentfractures, of whom 147 had fractures in common osteoporotic sites(hip, wrist or forearm, or vertebrae). Relative risks in the vitaminD group compared with the placebo group were 0.78 (95% confidenceinterval 0.61 to 0.99, P=0.04) for any first fracture and 0.67(0.48 to 0.93, P=0.02) for first hip, wrist or forearm, or vertebralfracture. 471 participants died. The relative risk for total mortalityin the vitamin D group compared with the placebo group was 0.88(0.74 to 1.06, P=0.18). Findings were consistent in men and womenand in doctors and the general practicepopulation.
Conclusion: Four monthly supplementation with 100 000IU oral vitamin D may prevent fractures without adverse effectsin men and women living in the generalcommunity.

What is already known in this topic
Vitamin D and calcium supplements are effective in preventing fractures in elderly women

Whether isolated vitamin D supplementation prevents fractures is not clear

What this paper adds
Four monthly oral supplementation with 100 000 IU vitamin D reduces fractures in men and women aged over 65 living in the general community

Total fracture incidence was reduced by 22% and fractures in major osteoporotic sites by 33%


© 2003 BMJ Publishing Group Ltd

Relevant Articles

Randomised controlled trial of calcium and supplementation with cholecalciferol (vitamin D3) for prevention of fractures in primary care
Jill Porthouse, Sarah Cockayne, Christine King, Lucy Saxon, Elizabeth Steele, Terry Aspray, Mike Baverstock, Yvonne Birks, Jo Dumville, Roger Francis, Cynthia Iglesias, Suezann Puffer, Anne Sutcliffe, Ian Watt, and David J Torgerson
BMJ 2005 330: 1003. [Abstract] [Full Text] [PDF]
Vitamin D three times a year can prevent fractures
BMJ 2003 326: 0. [Full Text] [PDF]

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  • Allain, T. J. (2005). Vitamin D and fracture prevention–treatment still indicated but clarification needed. Age Ageing 34: 542-544 [Full text]
  • Rockell, J. E., Green, T. J., Skeaff, C. M., Whiting, S. J., Taylor, R. W., Williams, S. M., Parnell, W. R., Scragg, R., Wilson, N., Schaaf, D., Fitzgerald, E. D., Wohlers, M. W. (2005). Season and Ethnicity Are Determinants of Serum 25-Hydroxyvitamin D Concentrations in New Zealand Children Aged 5-14 y. J. Nutr. 135: 2602-2608 [Abstract] [Full text]
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  • Rosen, C. J. (2005). Postmenopausal Osteoporosis. NEJM 353: 595-603 [Full text]
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  • Aloia, J. F., Talwar, S. A., Pollack, S., Yeh, J. (2005). A Randomized Controlled Trial of Vitamin D3 Supplementation in African American Women. Arch Intern Med 165: 1618-1623 [Abstract] [Full text]
  • Heaney, R. P. (2005). To D or Not to D. IBMS BoneKEy 2: 28-31 [Full text]
  • Holick, M. F., Siris, E. S., Binkley, N., Beard, M. K., Khan, A., Katzer, J. T., Petruschke, R. A., Chen, E., de Papp, A. E. (2005). Prevalence of Vitamin D Inadequacy among Postmenopausal North American Women Receiving Osteoporosis Therapy. J. Clin. Endocrinol. Metab. 90: 3215-3224 [Abstract] [Full text]
  • Bischoff-Ferrari, H. A., Willett, W. C., Wong, J. B., Giovannucci, E., Dietrich, T., Dawson-Hughes, B. (2005). Fracture Prevention With Vitamin D Supplementation: A Meta-analysis of Randomized Controlled Trials. JAMA 293: 2257-2264 [Abstract] [Full text]
  • Porthouse, J., Cockayne, S., King, C., Saxon, L., Steele, E., Aspray, T., Baverstock, M., Birks, Y., Dumville, J., Francis, R., Iglesias, C., Puffer, S., Sutcliffe, A., Watt, I., Torgerson, D. J (2005). Randomised controlled trial of calcium and supplementation with cholecalciferol (vitamin D3) for prevention of fractures in primary care. BMJ 330: 1003- [Abstract] [Full text]
  • Dawson-Hughes, B. (2005). The Role of Vitamin D in Fracture Prevention. IBMS BoneKEy 2: 6-10 [Full text]
  • Venning, G. (2005). Recent developments in vitamin D deficiency and muscle weakness among elderly people. BMJ 330: 524-526 [Full text]
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  • Calvo, M. S., Whiting, S. J., Barton, C. N. (2005). Vitamin D Intake: A Global Perspective of Current Status. J. Nutr. 135: 310-316 [Abstract] [Full text]
  • Hollis, B. W. (2005). Circulating 25-Hydroxyvitamin D Levels Indicative of Vitamin D Sufficiency: Implications for Establishing a New Effective Dietary Intake Recommendation for Vitamin D. J. Nutr. 135: 317-322 [Abstract] [Full text]
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Rapid Responses:

Read all Rapid Responses

Vitamin D deficiency, lack of sunlight, multiple sclerosis
Peter K. Tun
bmj.com, 1 Mar 2003 [Full text]
Level of vitamin D (3) supplementation 100,000IU
Anne Woo
bmj.com, 1 Mar 2003 [Full text]
Re: Level of vitamin D (3) supplementation 100,000IU
Robert D Toon
bmj.com, 2 Mar 2003 [Full text]
Why no funding for a community trial?
Jim Page
bmj.com, 2 Mar 2003 [Full text]
100,000 IU of Vitamin D is a Lethal Dose for Many in our Community
Trevor G Marshall, PhD
bmj.com, 3 Mar 2003 [Full text]
How can Trivedi et al, Overlook the Possibility of Hypervitaminosis-D?
Belinda J Fenter
bmj.com, 3 Mar 2003 [Full text]
Safety of Vitamin D dose in used in fracture trial
Kay-Tee Khaw
bmj.com, 3 Mar 2003 [Full text]
A Therapy is Only Safe if it “Does No Harm”
Trevor G Marshall, PhD
bmj.com, 4 Mar 2003 [Full text]
Could vitamin D be of potential benefit in epileptic patients?
Mohammed S Rashid (BPharm MRPharmS)
bmj.com, 5 Mar 2003 [Full text]
Make sure to measure the correct ‘Vitamin D’- there are four of them
Trevor G Marshall
bmj.com, 6 Mar 2003 [Full text]
Potential Confounding Factors May Have Impacted on the Results
Henry Zeimer
bmj.com, 7 Mar 2003 [Full text]
Re: How can Trivedi et al, Overlook the Possibility of Hypervitaminosis-D?
Reinhold Vieth
bmj.com, 9 Mar 2003 [Full text]
Podiatrists administering vitamin D
Peter J Elton
bmj.com, 10 Mar 2003 [Full text]
Vitamin D, falls and fractures
Jugdeep K Dhesi, et al.
bmj.com, 16 Mar 2003 [Full text]
Vitamin D status in the population
Haakon E. Meyer
bmj.com, 18 Mar 2003 [Full text]
frail elderly patients and vitamin D
Michael D Stone
bmj.com, 22 Mar 2003 [Full text]
Annual injection
Mark D Oliver
bmj.com, 22 Mar 2003 [Full text]
Vitamin D for the over 65s
Lisa A Dunkley, et al.
bmj.com, 22 Mar 2003 [Full text]
Re: Vitamin D, falls and fractures
Andrew Herxheimer
bmj.com, 28 Mar 2003 [Full text]
Dose of vitamin D
John J Cannell, MD
bmj.com, 12 Apr 2003 [Full text]
The effect and administration of vitamin D.
Rauno J. Heikinheimo, et al.
bmj.com, 26 Apr 2003 [Full text]
Vitamin D and fractures
Montserrat Romera, et al.
bmj.com, 5 May 2003 [Full text]
disponivel em

http://www.bmj.com/cgi/content/abstract/326/7387/469

Vitamin D is ray of sunshine for multiple sclerosis patients

A vitamina D é uma luz para os pacientes de esclerose múltipla

O consumo de vitamina D elimina o risco de desenvolver esclerose multipla. Aos pacientes que apresentam baixos níveis de vitamina D no sangue, são administradas altas doses deste suplemento, evitando o aumento do número de pessoaas doentes.

Vitamin D is ray of sunshine for multiple sclerosis patients

Melanie Reid and Oliver Gillie
February 5, 2009

A scan image of the brain of a multiple sclerosis sufferer

An MRI scan of the brain of a multiple sclerosis sufferer

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Multiple sclerosis could be prevented through daily vitamin D supplements, scientists told The Times last night.The first causal link has been established between the “sunshine vitamin” and a gene that increases the risk of MS, raising the possibility that the debilitating auto-immune disease could be eradicated.George Ebers, Professor of Clinical Neurology at the University of Oxford, claimed that there was hard evidence directly relating both genes and the environment to the origins of MS.

His work suggests that vitamin D deficiency during pregnancy and childhood may increase the risk of a child developing the disease.

He has also established the possibility that genetic vulnerability to MS, apparently initiated by lack of vitamin D, may be passed through families.

These risks might plausibly be reduced by giving vitamin D supplements to pregnant woman and young children.

“I think it offers the potential for treatment which might prevent MS in the future,” Professor Ebers said.

“Our research has married two key pieces of the puzzle. The interaction of vitamin D with the gene is very specific and it seems most unlikely to be a coincidence of any kind.”

Warnings over sun exposure could now also be called into question – sunlight allows the body to produce the vitamin.

Professor Ebers said: “Serious questions now arise over the wisdom of current advice to limit sun exposure and avoid sunbathing. We also need to give better advice and help to the public on vitamin D supplements, particularly pregnant and nursing mothers.”

The news has momentous implications for Scotland and other northern countries, where the incidence of multiple sclerosis is the highest in the world. It will give added urgency to recent moves by Scotland’s Chief Medical Officer to consider recommending vitamin D supplements.

Deficiency in vitamin D, caused by lack of exposure to sunshine, has been increasingly linked to the cloudier climate in Scotland and other northern latitudes. The deficiency is twice as common among the Scots as it is amongst the English – and Orkney and Shetland have among the highest rates.

Studies have also shown that fewer people with MS are born in November and more in May, implicating a lack of sunshine during pregnancy.

The breakthrough comes after a groundswell of expert belief in the importance of vitamin D. Last November, at a conference organised by the Scottish Government, international experts urged vitamin D supplements for Scots to be tested “sooner rather than later” to find whether they could improve the nation’s health.

Researchers for the World Health Organisation said there should be large, randomised trials as there was strong evidence that increased daily intake of vitamin D could significantly improve health.

The seminar followed evidence, revealed in The Times, that Scotland’s poor health record has close links to vitamin D deficiency. Last September this newspaper reported evidence from scientists in Canada that children with early symptoms of multiple sclerosis have low levels of vitamin D.

Until now there has been no scientific proof of the links. However, Professor Ebers and his team have shown that vitamin D affects a particular genetic variant, identified as the one that increases the risk of developing MS threefold.

They suggest that a shortage of the vitamin alters this variant, thus preventing the immune system from functioning normally.

Professor Ebers said: “Whether it’s at the core of MS is going to take some further work, but it does look like a reasonably good chance.”

Last October Professor Ebers, in an article in The Times, backed the idea of distributing vitamin D supplements in Scotland to guard against conditions that may be linked to a deficiency, including MS.

“It is plausible that some 200 cases a year of MS might be prevented in Scotland alone by giving vitamin D to mothers and children,” he wrote.

“Over a trial duration of 25 years, 5,000 cases of this disease might be otherwise prevented.

“The economic impact of each person with MS is at least an extra million pounds during a lifetime.

“Over 25 years £5 billion is at issue in this disease without factoring in the human cost, the increasing rate of MS or inflation. A large-scale programme providing vitamin D could provide scientific evidence.”

Disease of the North: MS rates per 100,000 of the population

Canada 240

Scotland 150 – 200

Norway 110

England and Wales 90 – 110

Australia 78

Spain 59

Brazil 18

Sources: Atlas of Multiple Sclerosis; bandolier.com

Disponível em

http://www.timesonline.co.uk/tol/life_and_style/health/article5663483.ece

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