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  <front>
    <journal-meta>
      <journal-id journal-id-type="publisher-id">abc</journal-id>
      <journal-title-group>
        <journal-title>Arquivos Brasileiros de Cardiologia</journal-title>
        <abbrev-journal-title abbrev-type="publisher">Arq. Bras. Cardiol.</abbrev-journal-title>
      </journal-title-group>
      <issn pub-type="ppub">0066-782X</issn>
      <issn pub-type="epub">1678-4170</issn>
      <publisher>
        <publisher-name>Sociedade Brasileira de Cardiologia - SBC</publisher-name>
        <publisher-loc>S&#227;o Paulo, SP, Brazil</publisher-loc>
      </publisher>
    </journal-meta>
    <article-meta>
      <article-id pub-id-type="publisher-id" specific-use="scielo-v3">X6PzcdnLgxFpbzYbRBWKM7G</article-id>
      <article-id pub-id-type="other">00010</article-id>
      <article-id pub-id-type="publisher-id" specific-use="scielo-v2">S0066-782X2009000800010</article-id>
      <article-id pub-id-type="publisher-id" specific-use="scielo-v1">S0066-782X(09)09300210</article-id>
      <article-id pub-id-type="doi">10.1590/S0066-782X2009000800010</article-id>
      <article-categories>
        <subj-group subj-group-type="heading">
          <subject>Artigos Originais</subject>
        </subj-group>
      </article-categories>
      <title-group>
        <article-title>Estudo prospectivo, duplo cego e cruzado da Camellia sinensis (ch&#225; verde) nas dislipidemias</article-title>
      </title-group>
      <contrib-group>
        <contrib contrib-type="author">
          <name>
            <surname>Batista</surname>
            <given-names>Gesiani de Almeida Pierin</given-names>
          </name>
          <xref ref-type="aff" rid="aff01"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Cunha</surname>
            <given-names>Cl&#225;udio L. Pereira da</given-names>
          </name>
          <xref ref-type="aff" rid="aff01"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Scartezini</surname>
            <given-names>Maril&#233;ia</given-names>
          </name>
          <xref ref-type="aff" rid="aff01"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>von der Heyde</surname>
            <given-names>Raul</given-names>
          </name>
          <xref ref-type="aff" rid="aff01"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Bitencourt</surname>
            <given-names>Mur&#237;lo G</given-names>
          </name>
          <xref ref-type="aff" rid="aff01"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Melo</surname>
            <given-names>Sandra Fabr&#237;cio de</given-names>
          </name>
          <xref ref-type="aff" rid="aff01"/>
        </contrib>
      </contrib-group>
      <aff id="aff01">
        <addr-line>
          <named-content content-type="state">Paran&#225;</named-content>
        </addr-line>
        <institution content-type="orgname">Universidade Federal do Paran&#225;</institution>
        <country country="BR">Brazil</country>
      </aff>
      <pub-date date-type="collection" publication-format="electronic">
        <month>08</month>
        <year>2009</year>
      </pub-date>
      <volume>93</volume>
      <issue>2</issue>
      <fpage>128</fpage>
      <lpage>134</lpage>
      <history>
        <date date-type="accepted">
          <day>14</day>
          <month>11</month>
          <year>2008</year>
        </date>
        <date date-type="rev-recd">
          <day>22</day>
          <month>10</month>
          <year>2008</year>
        </date>
        <date date-type="received">
          <day>21</day>
          <month>08</month>
          <year>2008</year>
        </date>
      </history>
      <permissions>
        <license license-type="open-access" xlink:href="http://creativecommons.org/licenses/by-nc/4.0/" xml:lang="en">
          <license-p>This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.</license-p>
        </license>
      </permissions>
      <abstract>
        <p>FUNDAMENTO: Estudos epidemiol&#243;gicos estabeleceram uma associa&#231;&#227;o entre dislipidemias e aterosclerose. A terapia nutricional &#233; um ponto central da estrat&#233;gia preventiva em indiv&#237;duos que apresentam fatores de risco para doen&#231;a ateroscler&#243;tica. OBJETIVOS: Investigar os efeitos do ch&#225; verde (Camellia sinensis) em pacientes portadores de dislipidemias. M&#201;TODOS: O estudo envolveu 33 pacientes, com idade entre 21 e 71 anos, que consumiam uma dieta com baixo teor de gorduras (25% a 35% das calorias totais e 200 mg de colesterol por dia). Foram randomizados para dois tratamentos sequenciais: c&#225;psulas contendo 250 mg de extrato seco do ch&#225; verde ou placebo, administradas por um per&#237;odo total de 16 semanas, tendo cada paciente utilizado ch&#225; verde (Camellia sinensis) por oito semanas e placebo em igual per&#237;odo. RESULTADOS: Os valores lip&#237;dicos basais (mg/dl) foram os seguintes: HDL-colesterol 60,7 &#177; 7,3; colesterol total 255 &#177; 30,9; LDL-colesterol 158,8 &#177; 29,0; triglicer&#237;deos 169,0 &#177; 61,3 e Apo-B 120,2 &#177; 18,9. As varia&#231;&#245;es lip&#237;dicas m&#233;dias, provocadas pelo uso do ch&#225; verde (Camellia sinensis), mostraram uma redu&#231;&#227;o de 3,9 % (p = 0,006) nas concentra&#231;&#245;es do colesterol total e uma redu&#231;&#227;o de 4,5 % (p = 0,026) do LDL-colesterol. A ingest&#227;o de ch&#225; verde n&#227;o influenciou significativamente os n&#237;veis de HDL-colesterol, dos triglicer&#237;deos e do Apo-B. Resultados n&#227;o significativos foram observados na avalia&#231;&#227;o dos lip&#237;deos sangu&#237;neos (colesterol total e LDL-colesterol) com o uso do placebo. CONCLUS&#195;O: Foi demonstrado o efeito ben&#233;fico do ch&#225; verde (Camellia sinensis), que reduziu significativamente, em oito semanas, os n&#237;veis de colesterol total e LDL-colesterol nesse grupo de pacientes.</p>
      </abstract>
      <kwd-group xml:lang="pt" kwd-group-type="author-generated">
        <kwd>Estudos epidemiol&#243;gicos</kwd>
        <kwd>estudos de casos e controles</kwd>
        <kwd>ch&#225; verde</kwd>
        <kwd>Camellia sinensis</kwd>
        <kwd>fitoterapia</kwd>
        <kwd>dislipidemias</kwd>
      </kwd-group>
      <pub-date publication-format="electronic" date-type="pub">
        <day>13</day>
        <month>10</month>
        <year>2009</year>
      </pub-date>
    </article-meta>
  </front>
  <body>
    <p>ARTIGO ORIGINAL </p>
    <p> DISLIPIDEMIAS</p>
    <p>Estudo prospectivo, duplo cego e cruzado da Camellia sinensis (ch&#225; verde) nas dislipidemias</p>
    <p>
      <bold>Gesiani de Almeida Pierin Batista; Cl&#225;udio L. Pereira da Cunha; Maril&#233;ia Scartezini; Raul von der Heyde; Mur&#237;lo G Bitencourt; Sandra Fabr&#237;cio de Melo</bold>
    </p>
    <p> Universidade Federal do Paran&#225;, PR - Brasil</p>
    <p>
      <xref ref-type="corresp" rid="nt02">Correspond&#234;ncia</xref>
    </p>
    <p>
      <bold>RESUMO</bold>
    </p>
    <p><bold>FUNDAMENTO: </bold>Estudos epidemiol&#243;gicos estabeleceram uma associa&#231;&#227;o entre dislipidemias e aterosclerose. A terapia nutricional &#233; um ponto central da estrat&#233;gia preventiva em indiv&#237;duos que apresentam fatores de risco para doen&#231;a ateroscler&#243;tica. </p>
    <p><bold>OBJETIVOS: </bold>Investigar os efeitos do ch&#225; verde (Camellia sinensis) em pacientes portadores de dislipidemias. </p>
    <p><bold>M&#201;TODOS: </bold>O estudo envolveu 33 pacientes, com idade entre 21 e 71 anos, que consumiam uma dieta com baixo teor de gorduras (25% a 35% das calorias totais e 200 mg de colesterol por dia). Foram randomizados para dois tratamentos sequenciais: c&#225;psulas contendo 250 mg de extrato seco do ch&#225; verde ou placebo, administradas por um per&#237;odo total de 16 semanas, tendo cada paciente utilizado ch&#225; verde (Camellia sinensis) por oito semanas e placebo em igual per&#237;odo. </p>
    <p><bold>RESULTADOS: </bold>Os valores lip&#237;dicos basais (mg/dl) foram os seguintes: HDL-colesterol 60,7 &#177; 7,3; colesterol total 255 &#177; 30,9; LDL-colesterol 158,8 &#177; 29,0; triglicer&#237;deos 169,0 &#177; 61,3 e Apo-B 120,2 &#177; 18,9. As varia&#231;&#245;es lip&#237;dicas m&#233;dias, provocadas pelo uso do ch&#225; verde (Camellia sinensis), mostraram uma redu&#231;&#227;o de 3,9 % (p = 0,006) nas concentra&#231;&#245;es do colesterol total e uma redu&#231;&#227;o de 4,5 % (p = 0,026) do LDL-colesterol. A ingest&#227;o de ch&#225; verde n&#227;o influenciou significativamente os n&#237;veis de HDL-colesterol, dos triglicer&#237;deos e do Apo-B. Resultados n&#227;o significativos foram observados na avalia&#231;&#227;o dos lip&#237;deos sangu&#237;neos (colesterol total e LDL-colesterol) com o uso do placebo. </p>
    <p><bold>CONCLUS&#195;O: </bold>Foi demonstrado o efeito ben&#233;fico do ch&#225; verde (Camellia sinensis), que reduziu significativamente, em oito semanas, os n&#237;veis de colesterol total e LDL-colesterol nesse grupo de pacientes.</p>
    <p><bold>Palavras-chave: </bold>Estudos epidemiol&#243;gicos, estudos de casos e controles, ch&#225; verde, Camellia sinensis, fitoterapia, dislipidemias.</p>
    <p>
      <bold>Introdu&#231;&#227;o</bold>
    </p>
    <p>O ch&#225; verde (<italic>Camellia sinensis</italic>) &#233; uma das bebidas mais antigas do mundo. O h&#225;bito de consumir o ch&#225; &#233; referido desde a antiguidade, quando as plantas eram utilizadas como medicamentos, tanto na preven&#231;&#227;o como no tratamento de dist&#250;rbios, disfun&#231;&#245;es ou doen&#231;as em seres humanos e animais<sup>1-3</sup>.Nos &#250;ltimos anos, uma crescente aten&#231;&#227;o tem sido dada ao uso do ch&#225; verde na promo&#231;&#227;o da sa&#250;de humana. A redu&#231;&#227;o nas concentra&#231;&#245;es sangu&#237;neas do colesterol total e do LDL-colesterol, por meio do consumo desse ch&#225;, tem sido repetidamente demonstrada em diversos estudos<sup>4-6</sup>.Por&#233;m, os componentes do ch&#225; verde respons&#225;veis por essas altera&#231;&#245;es ainda n&#227;o est&#227;o bem esclarecidos. Recentemente, alguns estudos postularam que os flavon&#243;ides do ch&#225; verde (catequinas), em especial a epigalocatequina gallate (EGCG), devido &#224; sua alta concentra&#231;&#227;o de polifen&#243;is antioxidantes, possa ser respons&#225;vel pela a&#231;&#227;o ben&#233;fica<sup>7-12</sup> do ch&#225;. Acredita-se ainda que os flavon&#243;ides do ch&#225; sejam efetivos antioxidantes e possam proteger o organismo contra diversas doen&#231;as cr&#244;nicas, principalmente as doen&#231;as cardiovasculares.Partindo da observa&#231;&#227;o que o consumo de alimentos ricos em flavon&#243;ides contribui para a redu&#231;&#227;o do risco cardiovascular, o desenho deste estudo teve por objetivo avaliar o ch&#225; verde como componente da dieta, al&#233;m de sua rela&#231;&#227;o sobre os perfis lip&#237;dicos sangu&#237;neos no tratamento de preven&#231;&#227;o prim&#225;ria em pacientes portadores de dislipidemias.</p>
    <p>O ch&#225; verde tem origem na regi&#227;o sul da China e &#233; cultivado na &#193;sia e nos pa&#237;ses da &#193;frica Central. Na China, o ch&#225; &#233; consumido h&#225; mais de tr&#234;s mil anos, sendo esse pa&#237;s o seu principal produtor. No Jap&#227;o, seu consumo come&#231;ou por meio dos monges budistas nos anos 800 d.C.<sup>13</sup>. O extrato de ch&#225; &#233; um produto sol&#250;vel em &#225;gua obtido por infus&#227;o. Os tr&#234;s principais tipos de ch&#225; s&#227;o o preto, o oolong e o verde. O ch&#225; verde, n&#227;o fermentado, &#233; produzido a partir das folhas frescas da planta <italic>Camellia sinensis</italic>, que cont&#233;m: &#225;gua, prote&#237;nas, hidratos de carbono, minerais, vitaminas e polifen&#243;is do tipo flavon&#243;ides. Os principais flavon&#243;ides do ch&#225; verde s&#227;o as catequinas epigalocatequina gallate (EGCG), as quais constituem um ter&#231;o1/3 do peso seco total. Esse ch&#225; &#233; pouco arom&#225;tico, tem sabor amargo e a infus&#227;o &#233; esverdeada, sendo tamb&#233;m conhecido como Thea sinensis. J&#225; o ch&#225; preto, ch&#225; de fermenta&#231;&#227;o completa, inclui em sua manufatura uma oxida&#231;&#227;o enzim&#225;tica, na qual a maioria das catequinas (polifen&#243;is) se converte em produtos de condensa&#231;&#227;o complexos (teaflavinos, tearubigina). E por fim, o ch&#225; oolong &#233; semifermentado e elaborado principalmente na China e em Taiwan<sup>14</sup>.</p>
    <p>
      <bold>M&#233;todos</bold>
    </p>
    <p>Este estudo foi conduzido no ambulat&#243;rio de Dislipidemias do Hospital de Cl&#237;nicas da Universidade Federal do Paran&#225; (UFPR). Participaram 38 pacientes portadores de hipercolesterolemia, com idades entre 21 e 71 anos. A pesquisa foi aprovada pelo Comit&#234; de &#201;tica em Pesquisa em Seres Humanos do Hospital de Cl&#237;nicas da UFPR, tendo sido obtido termo de consentimento livre e esclarecido de todos os participantes.</p>
    <p>
      <bold>Sele&#231;&#227;o dos pacientes</bold>
    </p>
    <p>Os crit&#233;rios utilizados para a inclus&#227;o dos pacientes no estudo foram: homens e mulheres acima de 20 anos de idade, sem evid&#234;ncia de doen&#231;a coronariana, com colesterol total (CT) &gt; 200 mg/dl e LDL-colesterol superior a 130 mg/dl. Exclu&#237;mos do estudo os pacientes portadores de insufici&#234;ncia renal ou hep&#225;tica, hipotireoidismo e diabete. Todos os participantes inclu&#237;dos no estudo foram submetidos ao exame cl&#237;nico e a avalia&#231;&#227;o nutricional. A medida da press&#227;o arterial foi feita pelos m&#233;todos palpat&#243;rio e ausculat&#243;rio, utilizando-se esfigmoman&#244;metro de coluna de merc&#250;rio, seguindo as orienta&#231;&#245;es das V Diretrizes Brasileira de Hipertens&#227;o Arterial<sup>15</sup>, em 2006.</p>
    <p>
      <bold>Avalia&#231;&#245;es</bold>
    </p>
    <p>Na avalia&#231;&#227;o nutricional utilizamos os m&#233;todos convencionais como a antropometria e o hist&#243;rico cl&#237;nico, familiar e diet&#233;tico. Avaliamos o peso, a estatura, o &#237;ndice de massa corporal (IMC), a composi&#231;&#227;o corporal, por meio de bioimped&#226;ncia el&#233;trica (BIA), e a circunfer&#234;ncia abdominal. Os h&#225;bitos alimentares foram avaliados por meio da frequ&#234;ncia dos alimentos, recordat&#243;rio alimentar de 24h e registro alimentar de tr&#234;s dias. Com base nesses dados, foram elaboradas as orienta&#231;&#245;es nutricionais individualizadas para todos os pacientes, sendo as mesmas monitoradas mensalmente durante um per&#237;odo de 16 semanas.</p>
    <p>
      <bold>Desenho da dieta</bold>
    </p>
    <p>A prescri&#231;&#227;o diet&#233;tica consistiu na ingest&#227;o menor que 35% do total de quilocalorias na forma de lip&#237;dios totais, com menos de 7% de gordura saturada, quantidade igual ou inferior a 10% de gordura poliinsaturada, e at&#233; 20% de gordura monoinsaturada. A recomenda&#231;&#227;o de colesterol foi menos de 200 mg/dia, em conformidade com as orienta&#231;&#245;es do III National Cholesterol Education Program (NCEP)<sup>16</sup>. Todos os pacientes seguiram essa dieta basal durante 16 semanas, per&#237;odo pelo qual foram randomizados para receber um dos tratamentos, incluindo doses di&#225;rias de c&#225;psulas contendo 250 mg de extrato seco do ch&#225; verde (<italic>Camellia sinensis</italic>) ou placebo, a cada oito semanas. Por se tratar de um estudo cruzado e duplo-cego, tanto os participantes, como os pesquisadores, n&#227;o sabiam a ordem em que as subst&#226;ncias seriam administradas. Ap&#243;s oito semanas de tratamento, houve uma invers&#227;o: o grupo que estava recebendo o ch&#225; verde passou a receber o placebo e vice-versa, por mais oito semanas. Os pacientes tamb&#233;m foram orientados a n&#227;o utilizar quaisquer suplementos vitam&#237;nicos durante o per&#237;odo de investiga&#231;&#227;o. Foram ainda informados sobre a import&#226;ncia da ades&#227;o &#224; dieta e da necessidade da mudan&#231;a no estilo de vida (controle do peso, atividade f&#237;sica, abstin&#234;ncia de fumo e &#225;lcool). Houve monitora&#231;&#227;o dos n&#237;veis lip&#237;dicos, do colesterol total, do HDL-colesterol, do LDL-colesterol, dos triglic&#233;rides, da apolipoprote&#237;na B (Apo-B) e das modifica&#231;&#245;es no estilo de vida.</p>
    <p>
      <bold>Avalia&#231;&#227;o dos dados</bold>
    </p>
    <p>Os pacientes tiveram o seu perfil lip&#237;dico determinado ap&#243;s jejum alimentar de 12 a 14 horas. Os valores s&#233;ricos dos triglicer&#237;deos e do colesterol fracionado foram quantificados utilizando-se o m&#233;todo colorim&#233;trico enzim&#225;tico homog&#234;neo; o LDL-colesterol foi estimado pela f&#243;rmula de Friedewald<sup>17</sup> e, para a dosagem da apolipoprote&#237;na B (Apo-B), foi utilizado o kit Dade. A glicose foi dosada pelo m&#233;todo Picrate Alcaline Bayer e os valores de s&#243;dio e pot&#225;ssio obtidos por eletrodos &#237;ons seletivos.</p>
    <p>Os dados foram expressos em m&#233;dia &#177; erro padr&#227;o da m&#233;dia. Para a comprova&#231;&#227;o das vari&#225;veis, foram utilizados os seguintes testes: o param&#233;trico t de Sudent pareado e o n&#227;o-param&#233;trico Wilcoxon amostras pareadas (por meio do software Primer of Biostatistics). O n&#237;vel de signific&#226;ncia (probabilidade de signific&#226;ncia) adotado foi menor que 5% (p&lt;0,05).</p>
    <p>
      <bold>Resultados</bold>
    </p>
    <p>
      <bold>Dados demogr&#225;ficos</bold>
    </p>
    <p>No total, 33 pacientes conclu&#237;ram o estudo. O n&#237;vel de escolaridade predominante era de ensino fundamental, com renda familiar entre um e dois sal&#225;rios m&#237;nimos. O total de 84,8% dos pacientes eram do sexo feminino, contra 15,2% do sexo masculino. A idade m&#233;dia dos pacientes era de 55,4 &#177; 10,1 anos (variando entre 21 e 71 anos). As caracter&#237;sticas antropom&#233;tricas do grupo estudado est&#227;o relacionadas na <xref ref-type="table" rid="tab01">tabela 1</xref>.</p>
    <table-wrap id="tab01">
      <graphic xlink:href="1678-4170-abc-93-02-0128-00010-gt01.jpg"/></table-wrap>
    <p>Em rela&#231;&#227;o aos par&#226;metros antropom&#233;tricos, houve varia&#231;&#227;o de peso na avalia&#231;&#227;o geral do grupo. No per&#237;odo pr&#233;-ch&#225; (71,4&#177;15,8 kg) e p&#243;s-ch&#225; (70,2&#177;15,4 kg), foi observada a perda de peso em 1,7% (p=0,002) e a diminui&#231;&#227;o do IMC em 1,7% (p=0,002) enquanto os pacientes faziam uso do ch&#225; verde. Comparado com o per&#237;odo pr&#233;-placebo (70,6+-15,5 kg) e p&#243;s-placebo (69,9+-14,9), tamb&#233;m houve perda ponderal com signific&#226;ncia estat&#237;stica menos expressiva; a perda de peso foi de 1,1% (p=0,041) e a redu&#231;&#227;o do IMC de 1,1% (p=0,047). Os dados das press&#245;es arteriais sist&#243;lica e diast&#243;lica n&#227;o sofreram altera&#231;&#245;es significativas.</p>
    <p>Ao administrarmos durante oito semanas c&#225;psulas contendo extrato seco de ch&#225; verde (250 mg), observamos uma varia&#231;&#227;o significativa nos n&#237;veis de lip&#237;deos sangu&#237;neos, principalmente na redu&#231;&#227;o da LDL-c no plasma. Na avalia&#231;&#227;o do perfil lip&#237;dico (ver <xref ref-type="table" rid="a10tab02">tabela 2</xref>), em rela&#231;&#227;o &#224;s situa&#231;&#245;es pr&#233; e p&#243;s-ch&#225; e pr&#233; e p&#243;s-placebo, foi observado que: com a ingest&#227;o de ch&#225; houve a redu&#231;&#227;o do colesterol total (3,9%) (p=0,006) e a redu&#231;&#227;o do LDL (4,5%) (p=0,026). Tamb&#233;m nota-se a diminui&#231;&#227;o n&#227;o significativa do HDL (2,1%) (p=0,218) e o aumento n&#227;o significativo dos TG (7,5%) (p=0,807) e do APO-B (4,4%) (p=0,180). Com o placebo houve a diminui&#231;&#227;o n&#227;o significativa do colesterol total (2,6%) (p=0,168), do LDL (1,8%) (p=0,396), do HDL (4,2%) (p=0,080) e da APO-B (0,8%) (p=0,677), al&#233;m do aumento n&#227;o significativo do TG (1,9%) (p=0,733).</p>
    <p content-type="asset">
      <table-wrap id="a10tab02">
        <graphic xlink:href="1678-4170-abc-93-02-0128-00010-gt02.jpg"/></table-wrap>
    </p>
    <p>Com rela&#231;&#227;o aos efeitos da interven&#231;&#227;o diet&#233;tica, ap&#243;s 16 semanas de tratamento, as necessidades diet&#233;ticas estavam adequadas &#224;s recomenda&#231;&#245;es e as modifica&#231;&#245;es alimentares, obtidas por meio da dieta, tiveram influ&#234;ncia sobre o consumo de gorduras, principalmente na redu&#231;&#227;o significativa dos &#225;cidos graxos saturados. Os valores encontram-se na <xref ref-type="table" rid="a10tab03">tabela 3</xref>.</p>
    <p content-type="asset">
      <table-wrap id="a10tab03">
        <graphic xlink:href="1678-4170-abc-93-02-0128-00010-gt03.jpg"/></table-wrap>
    </p>
    <p>
      <bold>Discuss&#227;o</bold>
    </p>
    <p>As dislipidemias est&#227;o entre os mais importantes fatores de risco da doen&#231;a cardiovascular ateroscler&#243;tica. V&#225;rios estudos t&#234;m evidenciado que o combate &#224;s dislipidemias traz benef&#237;cios &#224; pacientes em diferentes riscos cardiovasculares, e que, atrav&#233;s das redu&#231;&#245;es das hipercolesterolemias, proporcionam-se efeitos ben&#233;ficos cada vez maiores na redu&#231;&#227;o de eventos coronarianos<sup>17-27</sup>. Desses estudos, avan&#231;os significativos foram obtidos no conhecimento e controle das dislipidemias.</p>
    <p>O programa de tratamento recomendado para as dislipidemias &#233; baseado na monitora&#231;&#227;o dos n&#237;veis dos lip&#237;deos sangu&#237;neos e na institui&#231;&#227;o de interven&#231;&#245;es no estilo de vida. Essas interven&#231;&#245;es compreendem h&#225;bitos alimentares saud&#225;veis, manuten&#231;&#227;o do peso ideal, atividade f&#237;sica regular e combate ao tabagismo. A interven&#231;&#227;o diet&#233;tica &#233; a primeira abordagem no tratamento de dislipidemias, devendo ser mantida mesmo havendo necessidade de interven&#231;&#227;o medicamentosa<sup>28-30</sup>.</p>
    <p>A American Heart Association (AHA) enfatiza o uso de uma dieta que inclua uma variedade de frutas, vegetais e gr&#227;os, pois esses alimentos podem reduzir o risco de doen&#231;as cardiovasculares, por meio da oferta de vitaminas, nutrientes antioxidantes (flavon&#243;ides), fitoqu&#237;micos e fibras neles contidos<sup>16</sup>.</p>
    <p>No presente estudo, a interven&#231;&#227;o diet&#233;tica adotada nos permitiu avaliar os efeitos do ch&#225; verde conjuntamente com uma dieta adequada &#224;s recomenda&#231;&#245;es da AHA e do Programa Nacional de Educa&#231;&#227;o em Colesterol<sup>30</sup>, livre da interfer&#234;ncia pela varia&#231;&#227;o de outros nutrientes ou componentes da dieta.</p>
    <p>Com o prop&#243;sito de incluir o ch&#225; verde na dieta como interven&#231;&#227;o duplo cega, n&#227;o foi poss&#237;vel introduz&#237;-lo como bebida, devido &#224; dificuldade de monitorar a forma de preparo e a quantidade ingerida, tendo sido necess&#225;rio administr&#225;-lo na forma de c&#225;psula, o equivalente a quatro x&#237;caras de ch&#225; (150 ml) por dia.</p>
    <p>Neste estudo, ap&#243;s as interven&#231;&#245;es, as varia&#231;&#245;es lip&#237;dicas m&#233;dias provocadas pelo uso do ch&#225; verde (<italic>Camellia sinensis</italic>) sofreram uma redu&#231;&#227;o de 3,9 % (p = 0,006) nas concentra&#231;&#245;es de colesterol total e uma redu&#231;&#227;o de 4,5 % (p = 0,026) do LDL - colesterol. Essa quantidade de ch&#225; verde ingerida n&#227;o influenciou significativamente os n&#237;veis de HDL-c, dos triglicer&#237;deos e da Apo-B. Particularmente chamou aten&#231;&#227;o a aus&#234;ncia de varia&#231;&#227;o significativa da Apo-B, que n&#227;o acompanhou a redu&#231;&#227;o da LDL-c. Acredita-se que isto possa ser explicado pelo n&#250;mero reduzido de pacientes em um curto per&#237;odo de observa&#231;&#227;o, n&#227;o sendo poss&#237;vel observar essa diferen&#231;a com uma amostra desse tamanho. Do ponto de vista bioqu&#237;mico, poderia se ter como hip&#243;tese para justificar a aus&#234;ncia de varia&#231;&#227;o significativa da Apo-B, o fato do percentual de Apo-B nas lipoprote&#237;nas de baixa densidade ser menor que o percentual de LDL-colesterol e, nessa amostra pequena, a varia&#231;&#227;o n&#227;o foi expressiva. Sob uso do placebo, os n&#237;veis lip&#237;dicos n&#227;o apresentaram diferen&#231;as significativas.</p>
    <p>Apesar deste estudo envolver um n&#250;mero relativamente pequeno de volunt&#225;rios, nossos resultados s&#227;o condizentes com a primeira experimenta&#231;&#227;o cl&#237;nica em humanos, conduzida por Maron e cols. em 2003<sup>13</sup>, que avaliou 240 pessoas com dislipidemias internadas em hospitais da China. Os pesquisadores demonstraram, por meio de um estudo duplo-cego, com placebo-controlado, que os pacientes que haviam tomado c&#225;psulas contendo o extrato de ch&#225; por 12 semanas, apresentaram uma redu&#231;&#227;o de 11,3% das taxas do colesterol total e 16% das taxas do LDL-colesterol.</p>
    <p>Em outro estudo similar ao nosso, Davies e cols.<sup>31</sup> avaliaram o efeito do ch&#225; verde em 15 volunt&#225;rios adultos, com moderada hipercolesterolemia, conjuntamente com a ado&#231;&#227;o de uma dieta do tipo etapa I, como descrito pela American Heart Association e pelo Programa Nacional de Instru&#231;&#227;o do Colesterol. Ap&#243;s tr&#234;s semanas de tratamento, os investigadores chegaram a conclus&#227;o que cinco copos de ch&#225; por dia reduziram o colesterol total em 6,5% e a LDL-colesterol em 11,1%, em compara&#231;&#227;o &#224;s bebidas do placebo. Esses achados foram semelhantes aos identificados em nosso estudo.</p>
    <p>Em outro estudo, realizado em 2003, Kajimoto e cols.<sup>32</sup>, por meio de um experimento duplo-cego, mostraram que o tratamento com a ingest&#227;o de 395 mg/dia do ch&#225; verde reduziu significativamente os n&#237;veis de colesterol total, ap&#243;s oito semanas de administra&#231;&#227;o em pacientes com hipercolesterolemia moderada, o que n&#227;o foi observado no grupo do placebo. Mais recentemente, em outro desenho, conduzido por Kajimoto<sup>33</sup>, o tratamento com doses mais elevadas do ch&#225; (666 mg/dia) produziu uma diminui&#231;&#227;o adicional no colesterol total em compara&#231;&#227;o ao grupo que consumia 444 mg/dia, apesar de ambos os grupos demonstrarem diminui&#231;&#245;es significativas no colesterol total e no LDL-colesterol.</p>
    <p>No estudo realizado por Tokunaga e cols. em 2002<sup>4</sup>, com 13.916 indiv&#237;duos japoneses, o consumo de ch&#225; verde foi associado com a redu&#231;&#227;o dos n&#237;veis s&#233;ricos de colesterol, quando esse consumo perfazia mais de 10 x&#237;caras por dia. Por&#233;m, quando se relacionava com os aspectos de estilo de vida da popula&#231;&#227;o (tabagismo, uso de caf&#233; e &#225;lcool), IMC e idade, a redu&#231;&#227;o do colesterol j&#225; foi observada com a ingest&#227;o de apenas uma x&#237;cara de ch&#225; por dia. Diversos outros estudos tamb&#233;m evidenciaram o efeito ben&#233;fico do ch&#225; na redu&#231;&#227;o das doen&#231;as cardiovasculares<sup>32,34</sup>.</p>
    <p>Apesar dos nossos resultados terem revelado que o consumo de ch&#225; verde na dieta contribuiu para a redu&#231;&#227;o das gorduras sangu&#237;neas, n&#227;o foi poss&#237;vel avaliar os mecanismos pelos quais os flavon&#243;ides produzem tal efeito, n&#227;o sendo esse, todavia, o objetivo desta pesquisa.</p>
    <p>Al&#233;m disso, outro benef&#237;cio atribu&#237;do ao consumo do ch&#225; verde foi identificado em rela&#231;&#227;o aos par&#226;metros antropom&#233;tricos: observou-se perda de peso de 1,7 % (p=0,002) e diminui&#231;&#227;o do IMC de 1,7 % (p=0,002). No grupo placebo, a varia&#231;&#227;o foi significativa mas de menor intensidade, a perda de peso foi de 1,1% (p=0,041) e o IMC teve uma redu&#231;&#227;o de 1,1% (p=0,047).</p>
    <p>O controle do peso &#233; um fator importante, principalmente em pacientes com riscos cardiovasculares. Dois estudos importantes avaliam o efeito termog&#234;nico do ch&#225; em seres humanos. Em 1999, Dulloo e cols.<sup>35</sup> relataram o efeito do extrato de ch&#225; verde contendo cafe&#237;na e polifen&#243;is, no aumento do gasto energ&#233;tico de 24 horas e na oxida&#231;&#227;o de gordura em jovens saud&#225;veis. Dose equivalente de cafe&#237;na n&#227;o provocou o mesmo efeito, e os pesquisadores sugeriram que os polifen&#243;is do ch&#225; foram respons&#225;veis pelo resultado.</p>
    <p>Em outro estudo, Chantre e Lairon<sup>36</sup> tamb&#233;m demonstraram que o ch&#225; verde provocou emagrecimento e atribu&#237;ram este efeito ao aumento da termog&#234;nese. Ap&#243;s tr&#234;s meses de interven&#231;&#227;o, os autores observaram que houve uma redu&#231;&#227;o de 4,48% na circunfer&#234;ncia abdominal e de 4,6% na redu&#231;&#227;o do peso.</p>
    <p>A respeito dos outros componentes da dieta, ap&#243;s 16 semanas de tratamento, as necessidades diet&#233;ticas estavam adequadas &#224;s recomenda&#231;&#245;es do NCEP - ATP III<sup>16</sup>. As modifica&#231;&#245;es alimentares, obtidas atrav&#233;s da dieta, tiveram influ&#234;ncia sobre o consumo de gorduras, principalmente na redu&#231;&#227;o dos &#225;cidos graxos saturados. Houve uma diminui&#231;&#227;o bastante significativa da ingest&#227;o do valor cal&#243;rico total (p=0,0001), a diminui&#231;&#227;o do consumo de gorduras totais, de gorduras saturadas e do colesterol (p=0,0001) e o aumento do consumo de fibras (p=0,0001). Evidenciamos tamb&#233;m um aumento no consumo de prote&#237;nas (p=0,0001). Uma explica&#231;&#227;o para isso pode ser a restri&#231;&#227;o de alimentos gordurosos (carne bovina e seus derivados, gorduras <italic>trans</italic> e frituras em geral), sendo os mesmos substitu&#237;dos por outras fontes, incluindo o grupo do leite e seus derivados desnatados, bem como o uso da prote&#237;na de soja.</p>
    <p>Torna-se cada vez mais claro o potencial dos flavon&#243;ides na preven&#231;&#227;o das doen&#231;as cardiovasculares. Suas subst&#226;ncias biologicamente ativas possuem efeito redutor sobre o colesterol LDL, compar&#225;vel ou maior que o obtido com dietas baixas em gorduras saturadas e colesterol. Apesar de n&#227;o existirem demonstra&#231;&#245;es por ensaios cl&#237;nicos randomizados de que essas subst&#226;ncias de origem vegetal reduzam a morbimortalidade cardiovascular, acredita-se que esses alimentos possam fazer parte regular de uma alimenta&#231;&#227;o cardioprotetora.</p>
    <p>
      <bold>Conclus&#227;o</bold>
    </p>
    <p>Esses achados mostram os benef&#237;cios do ch&#225; verde <italic>(Camellia sinensis</italic>), em concord&#226;ncia com estudos pr&#233;vios da literatura, mas revelam tamb&#233;m que ainda s&#227;o necess&#225;rias novas investiga&#231;&#245;es, com maior n&#250;mero de pacientes e per&#237;odos de observa&#231;&#227;o mais longos, para validar as observa&#231;&#245;es iniciais feita neste estudo.</p>
    <p>
      <bold>Potencial Conflito de Interesses</bold>
    </p>
    <p>Declaro n&#227;o haver conflito de interesses pertinentes.</p>
    <p>
      <bold>Fontes de Financiamento</bold>
    </p>
    <p>O presente estudo foi financiado pela Universidade Federal do Paran&#225; e parcialmente financiado pelo Laborat&#243;rio de Manipula&#231;&#227;o Bio Store.</p>
    <p>
      <bold>Vincula&#231;&#227;o Acad&#234;mica</bold>
    </p>
    <p>Este artigo &#233; parte de tese de mestrado de Gesiani de Almeida Pierin Batista pela Universidade Federal do Paran&#225;.</p>
    <p>
      <bold>Refer&#234;ncias</bold>
    </p>
    <p content-type="ref-to-delete">1. Korolkovas A. A riqueza potencial de nossa flora. Rev Bras Farmacognosia. 1996; 1: 1-7. </p>
    <p content-type="ref-to-delete">2. Rates SMK. Plants as source of drugs. Toxicon. 2001; 39: 603-13. </p>
    <p content-type="ref-to-delete">3. Maron DJ, Sibilo GL, Sheng CN, Swu ZG, Li YH, Chen H, et al. Cholesterol-lowering effect of a theaflavin-enriched green tea extract: a randomized controlled trial. Arch Intern Med. 2003; 163: 1448-53. </p>
    <p content-type="ref-to-delete">4. Tokunaga S, White IR, Frost C, Tanaka K, Kono S. Green tea consumption and serum lipids and lipoproteins in a population of healthy workers in Japan. Ann Epidemiol. 2002; 12: 157-65.  </p>
    <p content-type="ref-to-delete">5. Hertog MG, Kromhout D, Aravanis C, Blackburn H, Buzina R, Fidanza F, et al. Flavonoid intake and long-term risk of coronary heart disease and cancer in the seven countries study. Arch Intern Med. 1995; 155 (4): 381-6.  </p>
    <p content-type="ref-to-delete">6. Mukamal KJ, Maclure M, Muller JE. Tea consumption and mortality after acute myocardial infarction. Circulation. 2002; 105: 2476-81. </p>
    <p content-type="ref-to-delete">7. Hodgson JM, Puddey IB, Croft KD. Acute effects of ingestion of black and green tea on lipoprotein oxidation. Am J Clin Nutr. 2000; 71 (5): 1103-7. </p>
    <p content-type="ref-to-delete">8. Leung LK, Su RCY, Zesheng Z, Huang Y, Chen ZY. Theaflavins in black and catechins in green tea are equally effective antioxidants. J Nutr. 2001; 131: 2248-51. </p>
    <p content-type="ref-to-delete">9. Hodgson JM, Croft KD, Mori TA, Burke V, Beilin LJ, Puddley IB. Regular ingestion of tea does not inhibit in vivo lipid peroxidation in humans. J Nutr. 2002; 132: 55-8. </p>
    <p content-type="ref-to-delete">10. Duffy SJ, Vita JA, Holbrook M, Swerdloff PL, Keaney JF Jr. Effect of acute and chronic tea consumption on platelet aggregation in patients with coronary artery disease. Arterioscler Thromb Vasc Biol. 2001; 21 (6): 1084-9. </p>
    <p content-type="ref-to-delete">11. Simin L, Manson JAE, Lee IM, Cole SR, Hennekens CH, Willett WC, et al. Fruit and vegetable intake and risk of cardiovascular disease: the Women's Health Study. Am J Clin Nutr. 2000; 72: 922-8. </p>
    <p content-type="ref-to-delete">12. Siddiqui IA, Afaq F, Adhami VM, Ahmad N, Mukhtar H. Antioxidants of the beverage tea in promotion of human health. Antioxid Redox Signal. 2004; 6 (3): 571-82. </p>
    <p content-type="ref-to-delete">13. Chopra D. The Chopra Center Herbal Handbook. USA: Three Rivers Press; 2000. </p>
    <p content-type="ref-to-delete">14. Ody P. The Herb Society's complete medicinal herbal. London: Dorling Kindersley; 1993. </p>
    <p content-type="ref-to-delete">15. Sociedade Brasileira de Cardiologia. Sociedade Brasileira de Hipertens&#227;o. V Diretrizes Brasileiras de Hipertens&#227;o arterial. 2006. (on line). [acesso em 2007 setembro 10]. Dispon&#237;vel em: <ext-link ext-link-type="uri" xlink:href="http://publicacoes.cardiol.br/consenso/2006/VDiretriz-HA.pdf">http://publicacoes.cardiol.br/consenso/2006/VDiretriz-HA.pdf</ext-link> </p>
    <p content-type="ref-to-delete">16. Third Report of the National Cholesterol Education Program (NCEP). Expert panel on detection, evaluation, and treatment of high blood cholesterol in adults (Adult Treatment Panel III) National Cholesterol Education Program (NCEP). Expert panel on Detection, Evaluation and Treatment of High Blood Cholesterol in adults. Circulation. 2002; 106 (25): 3143-421. </p>
    <p content-type="ref-to-delete">17. Santos RD, Sp&#243;sito AC, Santos JE, Fonseca FH, Moriguchi EH, Martinez TLR, et al. Programa de avalia&#231;&#227;o nacional do conhecimento sobre preven&#231;&#227;o da aterosclerose (PANDORA): como tem sido feito o tratamento das dislipidemias pelos m&#233;dicos brasileiros. Arq Bras Cardiol. 2000; 75: 289-95. </p>
    <p content-type="ref-to-delete">18. Santos Filho RD, Martinez TLR. Fatores de risco para doen&#231;a cardiovascular: velhos e novos fatores de risco, velhos problemas! Arq Bras Endocrinol Metab. 2002; 46 (3): 212-4. </p>
    <p content-type="ref-to-delete">19. Castelli WP. Cholesterol and lipids in the risk of coronary artery disease: the Framingham Heart Study. Can J Cardiol. 1998; 4 (Suppl A): 5A-10A. </p>
    <p content-type="ref-to-delete">20. Server PS, Dahlof B, Poulter NR, Wedel H, Beevers G, Caulfield M, et al. Prevention of coronary and stroke events with atorvastatin in hypertensive patients who have average or lower-than-average cholesterol concentrations, in the Anglo-Scandinavian Cardiac Outcomes Trial - Lipid Lowering Arm (ASCOT-LLA): a multicentre randomised controlled trial. Lancet. 2003; 361: 1149-58. </p>
    <p content-type="ref-to-delete">21. Kannel WB, Castelli WP, Gordon T. Serum cholesterol lipoproteins and of coronary heart disease: the Framinghan study. Ann Int Med. 1971; 74: 1-12. </p>
    <p content-type="ref-to-delete">22. Assmann G, Schulte H. Results and conclusions of the Prospective Cardiovascular Munster (PROCAM) Study. In: Assmann G. (ed). Lipid metabolism disorders and coronary heart disease. 2<sup>nd. </sup>ed. Stuttgart: FK Schattauer; 1993.  </p>
    <p content-type="ref-to-delete">23. Downs JR, Clearfield M, Weis S, Whitney E, Shapiro DR, Beere PA, et al. For the AFCAPS/TexCAPS Research Group. Primary prevention of acute coronary events with lovastatin in men and women with average cholesterol levels: results of AFCAPS/TexCAPS. JAMA. 1998; 279: 1615-22. </p>
    <p content-type="ref-to-delete">24. The Scandinavian Simvastatin Survival Study Group. Randomised trial of cholesterol lowering in 4,444 patients with coronary heart disease: the Scandinavian Simvatatin Survival Study (4S). Lancet. 1994; 344: 1383-9. </p>
    <p content-type="ref-to-delete">25. Shepherd J, Blauw GJ, Murphy MB. Pravastatin in elderly individuals at risk of vascular disease (PROSPER): a randomised controlled trial. PROspective Study of Pravastatin in the Elderly at Risk. Lancet. 2002; 360: 1623-30. </p>
    <p content-type="ref-to-delete">26. MRC/BHF heart protection study of cholesterol lowering with sinvastatin in 20536 high-risk individuals: a randomised placebo-controlled trial. Lancet. 2002; 360: 7-22.  </p>
    <p content-type="ref-to-delete">27. Grundy SM. Slide Atlas of lipid disorders. 3<sup>rd</sup>. ed. New York: Gower Medical Publishing; 1990.  </p>
    <p content-type="ref-to-delete">28. Kannel WB, Wilson PW, Nam BH, D'Agostino RB. Risk stratification of obesity as a coronary risk factor. Am J Cardiol. 2002; 90: 697-701. </p>
    <p content-type="ref-to-delete">29. Scott M, Grundy SM. Obesity, metabolic syndrome, and coronary atherosclerosis. Circulation. 2002; 105 (23): 2696-8. </p>
    <p content-type="ref-to-delete">30. Krause MV, Mahan LK. (eds.). Alimentos, nutri&#231;&#227;o e dietoterapia. 10&#170; ed. S&#227;o Paulo: Roca; 2002. </p>
    <p content-type="ref-to-delete">31. Davies MJ, Judd JT, Baer DJ, Clevidence BA, Paul DR, Edwards AJ, et al. Black tea consumption reduces total and LDL cholesterol in mildly hypercholesterolemic adults. J Nutr. 2003; 133: 3298S-3302S.  </p>
    <p content-type="ref-to-delete">32. Kajimoto O, Kajimoto Y, Yabune M, Nozawa A, Nagata K, Kakuda T. Tea catechins reduce serum cholesterol levels in mild borderline hypercholesterolemic patients. J Clin Biochem Nutr. 2003; 33: 101-11. </p>
    <p content-type="ref-to-delete">33. Kajimoto O, Kajimoto Y, Yabune M, Nakamura T, Kotani K, Suzuki Y, et al. Tea catechins with a galloyl moiety reduce body weight and fat. J Health Sci. 2005; 51: 161-71. </p>
    <p content-type="ref-to-delete">34. Geleijnse JM, Launer LJ, Van der Kuip DA, Hofman A, Witteman JC. Inverse association of tea and flavonoid intakes with incident myocardial infarction: the Rotterdam Study. Am J Clin Nutr. 2002; 75 (5): 880-6.  </p>
    <p content-type="ref-to-delete">35. Dulloo AG, Duret C, Rohrer D, Girardier L, Mensi N, Fathi M, et al. Efficacy of a green tea extract rich in catechin polyphenols and caffeine in increasing 24-h energy expenditure and fat oxidation in humans. Am J Clin Nutr. 1999; 70: 1040-5. </p>
    <p>36. Chantre P, Lairon D. Recent findings of green tea extract AR25 (Exolise) and its activity for the treatment of obesity. <bold>Phytomedicine. 2002; 9 (1): 3-8. </bold></p>
    <p>
      <fn id="nt02" fn-type="corresp">
        <p>Correspond&#234;ncia:</p>
        <p> Gesiani de Almeida Pierin Batista </p>
        <p> Rua Bar&#227;o do Rio Branco, 2013 / 02 - Centro </p>
        <p> 83750-000, Lapa, PR - Brasil </p>
        <p> Email: </p>
        <p>
          <email xlink:href="gesiani@uol.com.br">gesiani@uol.com.br</email>
        </p>
      </fn>
    </p>
    <p>Artigo recebido em 21/08/08; revisado recebido em 22/10/08; aceito em 14/11/08.</p>
  </body>
  <back>
    <ref-list>
      <ref id="B1">
        <mixed-citation>1. Korolkovas A. A riqueza potencial de nossa flora. Rev Bras Farmacognosia. 1996; 1: 1-7.</mixed-citation>
        <element-citation publication-type="journal">
          <article-title>A riqueza potencial de nossa flora</article-title>
          <source>Rev Bras Farmacognosia</source>
          <date>
            <year>1996</year>
          </date>
          <fpage>1</fpage>
          <lpage>7</lpage>
          <volume>1</volume>
          <person-group person-group-type="author">
            <name>
              <surname>Korolkovas</surname>
              <given-names>A</given-names>
            </name>
          </person-group>
        </element-citation>
      </ref>
      <ref id="B2">
        <mixed-citation>2. Rates SMK. Plants as source of drugs. Toxicon. 2001; 39: 603-13.</mixed-citation>
        <element-citation publication-type="journal">
          <article-title>Plants as source of drugs</article-title>
          <source>Toxicon</source>
          <date>
            <year>2001</year>
          </date>
          <fpage>603</fpage>
          <lpage>13</lpage>
          <volume>39</volume>
          <person-group person-group-type="author">
            <name>
              <surname>Rates</surname>
              <given-names>SMK</given-names>
            </name>
          </person-group>
        </element-citation>
      </ref>
      <ref id="B3">
        <mixed-citation>3. Maron DJ, Sibilo GL, Sheng CN, Swu ZG, Li YH, Chen H, et al. Cholesterol-lowering effect of a theaflavin-enriched green tea extract: a randomized controlled trial. Arch Intern Med. 2003; 163: 1448-53.</mixed-citation>
        <element-citation publication-type="journal">
          <article-title>Cholesterol-lowering effect of a theaflavin-enriched green tea extract: a randomized controlled trial</article-title>
          <source>Arch Intern Med</source>
          <date>
            <year>2003</year>
          </date>
          <fpage>1448</fpage>
          <lpage>53</lpage>
          <volume>163</volume>
          <person-group person-group-type="author">
            <name>
              <surname>Maron</surname>
              <given-names>DJ</given-names>
            </name>
            <name>
              <surname>Sibilo</surname>
              <given-names>GL</given-names>
            </name>
            <name>
              <surname>Sheng</surname>
              <given-names>CN</given-names>
            </name>
            <name>
              <surname>Swu</surname>
              <given-names>ZG</given-names>
            </name>
            <name>
              <surname>Li</surname>
              <given-names>YH</given-names>
            </name>
            <name>
              <surname>Chen</surname>
              <given-names>H</given-names>
            </name>
          </person-group>
        </element-citation>
      </ref>
      <ref id="B4">
        <mixed-citation>4. Tokunaga S, White IR, Frost C, Tanaka K, Kono S. Green tea consumption and serum lipids and lipoproteins in a population of healthy workers in Japan. Ann Epidemiol. 2002; 12: 157-65.</mixed-citation>
        <element-citation publication-type="journal">
          <article-title>Green tea consumption and serum lipids and lipoproteins in a population of healthy workers in Japan</article-title>
          <source>Ann Epidemiol</source>
          <date>
            <year>2002</year>
          </date>
          <fpage>157</fpage>
          <lpage>65</lpage>
          <volume>12</volume>
          <person-group person-group-type="author">
            <name>
              <surname>Tokunaga</surname>
              <given-names>S</given-names>
            </name>
            <name>
              <surname>White</surname>
              <given-names>IR</given-names>
            </name>
            <name>
              <surname>Frost</surname>
              <given-names>C</given-names>
            </name>
            <name>
              <surname>Tanaka</surname>
              <given-names>K</given-names>
            </name>
            <name>
              <surname>Kono</surname>
              <given-names>S</given-names>
            </name>
          </person-group>
        </element-citation>
      </ref>
      <ref id="B5">
        <mixed-citation>5. Hertog MG, Kromhout D, Aravanis C, Blackburn H, Buzina R, Fidanza F, et al. Flavonoid intake and long-term risk of coronary heart disease and cancer in the seven countries study. Arch Intern Med. 1995; 155 (4): 381-6.</mixed-citation>
        <element-citation publication-type="journal">
          <article-title>Flavonoid intake and long-term risk of coronary heart disease and cancer in the seven countries study</article-title>
          <source>Arch Intern Med</source>
          <date>
            <year>1995</year>
          </date>
          <fpage>381</fpage>
          <lpage>6</lpage>
          <issue>4</issue>
          <volume>155</volume>
          <person-group person-group-type="author">
            <name>
              <surname>Hertog</surname>
              <given-names>MG</given-names>
            </name>
            <name>
              <surname>Kromhout</surname>
              <given-names>D</given-names>
            </name>
            <name>
              <surname>Aravanis</surname>
              <given-names>C</given-names>
            </name>
            <name>
              <surname>Blackburn</surname>
              <given-names>H</given-names>
            </name>
            <name>
              <surname>Buzina</surname>
              <given-names>R</given-names>
            </name>
            <name>
              <surname>Fidanza</surname>
              <given-names>F</given-names>
            </name>
          </person-group>
        </element-citation>
      </ref>
      <ref id="B6">
        <mixed-citation>6. Mukamal KJ, Maclure M, Muller JE. Tea consumption and mortality after acute myocardial infarction. Circulation. 2002; 105: 2476-81.</mixed-citation>
        <element-citation publication-type="journal">
          <article-title>Tea consumption and mortality after acute myocardial infarction</article-title>
          <source>Circulation</source>
          <date>
            <year>2002</year>
          </date>
          <fpage>2476</fpage>
          <lpage>81</lpage>
          <volume>105</volume>
          <person-group person-group-type="author">
            <name>
              <surname>Mukamal</surname>
              <given-names>KJ</given-names>
            </name>
            <name>
              <surname>Maclure</surname>
              <given-names>M</given-names>
            </name>
            <name>
              <surname>Muller</surname>
              <given-names>JE</given-names>
            </name>
          </person-group>
        </element-citation>
      </ref>
      <ref id="B7">
        <mixed-citation>7. Hodgson JM, Puddey IB, Croft KD. Acute effects of ingestion of black and green tea on lipoprotein oxidation. Am J Clin Nutr. 2000; 71 (5): 1103-7.</mixed-citation>
        <element-citation publication-type="journal">
          <article-title>Acute effects of ingestion of black and green tea on lipoprotein oxidation</article-title>
          <source>Am J Clin Nutr</source>
          <date>
            <year>2000</year>
          </date>
          <fpage>1103</fpage>
          <lpage>7</lpage>
          <issue>5</issue>
          <volume>71</volume>
          <person-group person-group-type="author">
            <name>
              <surname>Hodgson</surname>
              <given-names>JM</given-names>
            </name>
            <name>
              <surname>Puddey</surname>
              <given-names>IB</given-names>
            </name>
            <name>
              <surname>Croft</surname>
              <given-names>KD</given-names>
            </name>
          </person-group>
        </element-citation>
      </ref>
      <ref id="B8">
        <mixed-citation>8. Leung LK, Su RCY, Zesheng Z, Huang Y, Chen ZY. Theaflavins in black and catechins in green tea are equally effective antioxidants. J Nutr. 2001; 131: 2248-51.</mixed-citation>
        <element-citation publication-type="journal">
          <article-title>Theaflavins in black and catechins in green tea are equally effective antioxidants</article-title>
          <source>J Nutr</source>
          <date>
            <year>2001</year>
          </date>
          <fpage>2248</fpage>
          <lpage>51</lpage>
          <volume>131</volume>
          <person-group person-group-type="author">
            <name>
              <surname>Leung</surname>
              <given-names>LK</given-names>
            </name>
            <name>
              <surname>Su</surname>
              <given-names>RCY</given-names>
            </name>
            <name>
              <surname>Zesheng</surname>
              <given-names>Z</given-names>
            </name>
            <name>
              <surname>Huang</surname>
              <given-names>Y</given-names>
            </name>
            <name>
              <surname>Chen</surname>
              <given-names>ZY</given-names>
            </name>
          </person-group>
        </element-citation>
      </ref>
      <ref id="B9">
        <mixed-citation>9. Hodgson JM, Croft KD, Mori TA, Burke V, Beilin LJ, Puddley IB. Regular ingestion of tea does not inhibit in vivo lipid peroxidation in humans. J Nutr. 2002; 132: 55-8.</mixed-citation>
        <element-citation publication-type="journal">
          <article-title>Regular ingestion of tea does not inhibit in vivo lipid peroxidation in humans</article-title>
          <source>J Nutr</source>
          <date>
            <year>2002</year>
          </date>
          <fpage>55</fpage>
          <lpage>8</lpage>
          <volume>132</volume>
          <person-group person-group-type="author">
            <name>
              <surname>Hodgson</surname>
              <given-names>JM</given-names>
            </name>
            <name>
              <surname>Croft</surname>
              <given-names>KD</given-names>
            </name>
            <name>
              <surname>Mori</surname>
              <given-names>TA</given-names>
            </name>
            <name>
              <surname>Burke</surname>
              <given-names>V</given-names>
            </name>
            <name>
              <surname>Beilin</surname>
              <given-names>LJ</given-names>
            </name>
            <name>
              <surname>Puddley</surname>
              <given-names>IB</given-names>
            </name>
          </person-group>
        </element-citation>
      </ref>
      <ref id="B10">
        <mixed-citation>10. Duffy SJ, Vita JA, Holbrook M, Swerdloff PL, Keaney JF Jr. Effect of acute and chronic tea consumption on platelet aggregation in patients with coronary artery disease. Arterioscler Thromb Vasc Biol. 2001; 21 (6): 1084-9.</mixed-citation>
        <element-citation publication-type="journal">
          <article-title>Effect of acute and chronic tea consumption on platelet aggregation in patients with coronary artery disease</article-title>
          <source>Arterioscler Thromb Vasc Biol</source>
          <date>
            <year>2001</year>
          </date>
          <fpage>1084</fpage>
          <lpage>9</lpage>
          <issue>6</issue>
          <volume>21</volume>
          <person-group person-group-type="author">
            <name>
              <surname>Duffy</surname>
              <given-names>SJ</given-names>
            </name>
            <name>
              <surname>Vita</surname>
              <given-names>JA</given-names>
            </name>
            <name>
              <surname>Holbrook</surname>
              <given-names>M</given-names>
            </name>
            <name>
              <surname>Swerdloff</surname>
              <given-names>PL</given-names>
            </name>
            <name>
              <surname>Keaney Jr</surname>
              <given-names>JF</given-names>
            </name>
          </person-group>
        </element-citation>
      </ref>
      <ref id="B11">
        <mixed-citation>11. Simin L, Manson JAE, Lee IM, Cole SR, Hennekens CH, Willett WC, et al. Fruit and vegetable intake and risk of cardiovascular disease: the Women's Health Study. Am J Clin Nutr. 2000; 72: 922-8.</mixed-citation>
        <element-citation publication-type="journal">
          <article-title>Fruit and vegetable intake and risk of cardiovascular disease: the Women's Health Study</article-title>
          <source>Am J Clin Nutr</source>
          <date>
            <year>2000</year>
          </date>
          <fpage>922</fpage>
          <lpage>8</lpage>
          <volume>72</volume>
          <person-group person-group-type="author">
            <name>
              <surname>Simin</surname>
              <given-names>L</given-names>
            </name>
            <name>
              <surname>Manson</surname>
              <given-names>JAE</given-names>
            </name>
            <name>
              <surname>Lee</surname>
              <given-names>IM</given-names>
            </name>
            <name>
              <surname>Cole</surname>
              <given-names>SR</given-names>
            </name>
            <name>
              <surname>Hennekens</surname>
              <given-names>CH</given-names>
            </name>
            <name>
              <surname>Willett</surname>
              <given-names>WC</given-names>
            </name>
          </person-group>
        </element-citation>
      </ref>
      <ref id="B12">
        <mixed-citation>12. Siddiqui IA, Afaq F, Adhami VM, Ahmad N, Mukhtar H. Antioxidants of the beverage tea in promotion of human health. Antioxid Redox Signal. 2004; 6 (3):   571-82.</mixed-citation>
        <element-citation publication-type="journal">
          <article-title>Antioxidants of the beverage tea in promotion of human health</article-title>
          <source>Antioxid Redox Signal</source>
          <date>
            <year>2004</year>
          </date>
          <fpage>571</fpage>
          <lpage>82</lpage>
          <issue>3</issue>
          <volume>6</volume>
          <person-group person-group-type="author">
            <name>
              <surname>Siddiqui</surname>
              <given-names>IA</given-names>
            </name>
            <name>
              <surname>Afaq</surname>
              <given-names>F</given-names>
            </name>
            <name>
              <surname>Adhami</surname>
              <given-names>VM</given-names>
            </name>
            <name>
              <surname>Ahmad</surname>
              <given-names>N</given-names>
            </name>
            <name>
              <surname>Mukhtar</surname>
              <given-names>H</given-names>
            </name>
          </person-group>
        </element-citation>
      </ref>
      <ref id="B13">
        <mixed-citation>13. Chopra D. The Chopra Center Herbal Handbook. USA: Three Rivers Press; 2000.</mixed-citation>
        <element-citation publication-type="book">
          <source>The Chopra Center Herbal Handbook</source>
          <date>
            <year>2000</year>
          </date>
          <person-group person-group-type="author">
            <name>
              <surname>Chopra</surname>
              <given-names>D</given-names>
            </name>
          </person-group>
        </element-citation>
      </ref>
      <ref id="B14">
        <mixed-citation>14. Ody P. The Herb Society's complete medicinal herbal. London: Dorling Kindersley; 1993.</mixed-citation>
        <element-citation publication-type="book">
          <source>The Herb Society's complete medicinal herbal</source>
          <date>
            <year>1993</year>
          </date>
          <person-group person-group-type="author">
            <name>
              <surname>Ody</surname>
              <given-names>P</given-names>
            </name>
          </person-group>
        </element-citation>
      </ref>
      <ref id="B15">
        <mixed-citation>15. Sociedade Brasileira de Cardiologia. Sociedade Brasileira de Hipertens&#227;o. V Diretrizes Brasileiras de Hipertens&#227;o arterial. 2006. (on line). [acesso em 2007 setembro 10]. Dispon&#237;vel em: <ext-link ext-link-type="uri" xlink:href="http://publicacoes.cardiol.br/consenso/2006/VDiretriz-HA.pdf">http://publicacoes.cardiol.br/consenso/2006/VDiretriz-HA.pdf</ext-link></mixed-citation>
        <element-citation publication-type="book">
          <source>V Diretrizes Brasileiras de Hipertens&#227;o arterial</source>
          <date>
            <year>2006</year>
          </date>
        </element-citation>
      </ref>
      <ref id="B16">
        <mixed-citation>16. Third Report of the National Cholesterol Education Program (NCEP). Expert panel on detection, evaluation, and treatment of high blood cholesterol in adults (Adult Treatment Panel III) National Cholesterol Education Program (NCEP). Expert panel on Detection, Evaluation and Treatment of High Blood Cholesterol in adults. Circulation. 2002; 106 (25): 3143-421.</mixed-citation>
        <element-citation publication-type="journal">
          <article-title>Expert panel on detection, evaluation, and treatment of high blood cholesterol in adults (Adult Treatment Panel III) National Cholesterol Education Program (NCEP): Expert panel on Detection, Evaluation and Treatment of High Blood Cholesterol in adults</article-title>
          <source>Circulation</source>
          <date>
            <year>2002</year>
          </date>
          <fpage>3143</fpage>
          <lpage>421</lpage>
          <issue>25</issue>
          <volume>106</volume>
        </element-citation>
      </ref>
      <ref id="B17">
        <mixed-citation>17. Santos RD, Sp&#243;sito AC, Santos JE, Fonseca FH, Moriguchi EH, Martinez TLR, et al. Programa de avalia&#231;&#227;o nacional do conhecimento sobre preven&#231;&#227;o da aterosclerose (PANDORA): como tem sido feito o tratamento das dislipidemias pelos m&#233;dicos brasileiros. Arq Bras Cardiol. 2000; 75: 289-95.</mixed-citation>
        <element-citation publication-type="journal">
          <article-title>Programa de avalia&#231;&#227;o nacional do conhecimento sobre preven&#231;&#227;o da aterosclerose (PANDORA): como tem sido feito o tratamento das dislipidemias pelos m&#233;dicos brasileiros</article-title>
          <source>Arq Bras Cardiol</source>
          <date>
            <year>2000</year>
          </date>
          <fpage>289</fpage>
          <lpage>95</lpage>
          <volume>75</volume>
          <person-group person-group-type="author">
            <name>
              <surname>Santos</surname>
              <given-names>RD</given-names>
            </name>
            <name>
              <surname>Sp&#243;sito</surname>
              <given-names>AC</given-names>
            </name>
            <name>
              <surname>Santos</surname>
              <given-names>JE</given-names>
            </name>
            <name>
              <surname>Fonseca</surname>
              <given-names>FH</given-names>
            </name>
            <name>
              <surname>Moriguchi</surname>
              <given-names>EH</given-names>
            </name>
            <name>
              <surname>Martinez</surname>
              <given-names>TLR</given-names>
            </name>
          </person-group>
        </element-citation>
      </ref>
      <ref id="B18">
        <mixed-citation>18. Santos Filho RD, Martinez TLR. Fatores de risco para doen&#231;a cardiovascular: velhos e novos fatores de risco, velhos problemas! Arq Bras Endocrinol Metab. 2002; 46 (3): 212-4.</mixed-citation>
        <element-citation publication-type="journal">
          <article-title>Fatores de risco para doen&#231;a cardiovascular: velhos e novos fatores de risco, velhos problemas!</article-title>
          <source>Arq Bras Endocrinol Metab</source>
          <date>
            <year>2002</year>
          </date>
          <fpage>212</fpage>
          <lpage>4</lpage>
          <issue>3</issue>
          <volume>46</volume>
          <person-group person-group-type="author">
            <name>
              <surname>Santos Filho</surname>
              <given-names>RD</given-names>
            </name>
            <name>
              <surname>Martinez</surname>
              <given-names>TLR</given-names>
            </name>
          </person-group>
        </element-citation>
      </ref>
      <ref id="B19">
        <mixed-citation>19. Castelli WP. Cholesterol and lipids in the risk of coronary artery disease: the Framingham Heart Study. Can J Cardiol. 1998; 4 (Suppl A): 5A-10A.</mixed-citation>
        <element-citation publication-type="journal">
          <article-title>Cholesterol and lipids in the risk of coronary artery disease: the Framingham Heart Study</article-title>
          <source>Can J Cardiol</source>
          <date>
            <year>1998</year>
          </date>
          <fpage>5A</fpage>
          <lpage>10A</lpage>
          <volume>4</volume>
          <person-group person-group-type="author">
            <name>
              <surname>Castelli</surname>
              <given-names>WP</given-names>
            </name>
          </person-group>
        </element-citation>
      </ref>
      <ref id="B20">
        <mixed-citation>20. Server PS, Dahlof B, Poulter NR, Wedel H, Beevers G, Caulfield M, et al. Prevention of coronary and stroke events with atorvastatin in hypertensive patients who have average or lower-than-average cholesterol concentrations, in the Anglo-Scandinavian Cardiac Outcomes Trial - Lipid Lowering Arm (ASCOT-LLA): a multicentre randomised controlled trial. Lancet. 2003; 361: 1149-58.</mixed-citation>
        <element-citation publication-type="journal">
          <article-title>Prevention of coronary and stroke events with atorvastatin in hypertensive patients who have average or lower-than-average cholesterol concentrations, in the Anglo-Scandinavian Cardiac Outcomes Trial - Lipid Lowering Arm (ASCOT-LLA): a multicentre randomised controlled trial</article-title>
          <source>Lancet</source>
          <date>
            <year>2003</year>
          </date>
          <fpage>1149</fpage>
          <lpage>58</lpage>
          <volume>361</volume>
          <person-group person-group-type="author">
            <name>
              <surname>Server</surname>
              <given-names>PS</given-names>
            </name>
            <name>
              <surname>Dahlof</surname>
              <given-names>B</given-names>
            </name>
            <name>
              <surname>Poulter</surname>
              <given-names>NR</given-names>
            </name>
            <name>
              <surname>Wedel</surname>
              <given-names>H</given-names>
            </name>
            <name>
              <surname>Beevers</surname>
              <given-names>G</given-names>
            </name>
            <name>
              <surname>Caulfield</surname>
              <given-names>M</given-names>
            </name>
          </person-group>
        </element-citation>
      </ref>
      <ref id="B21">
        <mixed-citation>21. Kannel WB, Castelli WP, Gordon T. Serum cholesterol lipoproteins and of coronary heart disease: the Framinghan study. Ann Int Med. 1971; 74: 1-12.</mixed-citation>
        <element-citation publication-type="journal">
          <article-title>Serum cholesterol lipoproteins and of coronary heart disease: the Framinghan study</article-title>
          <source>Ann Int Med</source>
          <date>
            <year>1971</year>
          </date>
          <fpage>1</fpage>
          <lpage>12</lpage>
          <volume>74</volume>
          <person-group person-group-type="author">
            <name>
              <surname>Kannel</surname>
              <given-names>WB</given-names>
            </name>
            <name>
              <surname>Castelli</surname>
              <given-names>WP</given-names>
            </name>
            <name>
              <surname>Gordon</surname>
              <given-names>T</given-names>
            </name>
          </person-group>
        </element-citation>
      </ref>
      <ref id="B22">
        <mixed-citation>22. Assmann G, Schulte H. Results and conclusions of the Prospective Cardiovascular Munster (PROCAM) Study. In: Assmann G. (ed). Lipid metabolism disorders and coronary heart disease. 2<sup>nd. </sup>ed. Stuttgart: FK Schattauer; 1993.</mixed-citation>
        <element-citation publication-type="book">
          <source>Lipid metabolism disorders and coronary heart disease</source>
          <date>
            <year>1993</year>
          </date>
          <person-group person-group-type="author">
            <name>
              <surname>Assmann</surname>
              <given-names>G</given-names>
            </name>
            <name>
              <surname>Schulte</surname>
              <given-names>H.</given-names>
            </name>
            <name>
              <surname>Assmann</surname>
              <given-names>G.</given-names>
            </name>
          </person-group>
        </element-citation>
      </ref>
      <ref id="B23">
        <mixed-citation>23. Downs JR, Clearfield M, Weis S, Whitney E, Shapiro DR, Beere PA, et al. For the AFCAPS/TexCAPS Research Group. Primary prevention of acute coronary events with lovastatin in men and women with average cholesterol levels: results of AFCAPS/TexCAPS. JAMA. 1998; 279: 1615-22.</mixed-citation>
        <element-citation publication-type="journal">
          <article-title>For the AFCAPS/TexCAPS Research Group. Primary prevention of acute coronary events with lovastatin in men and women with average cholesterol levels: results of AFCAPS/TexCAPS</article-title>
          <source>JAMA</source>
          <date>
            <year>1998</year>
          </date>
          <fpage>1615</fpage>
          <lpage>22</lpage>
          <volume>279</volume>
          <person-group person-group-type="author">
            <name>
              <surname>Downs</surname>
              <given-names>JR</given-names>
            </name>
            <name>
              <surname>Clearfield</surname>
              <given-names>M</given-names>
            </name>
            <name>
              <surname>Weis</surname>
              <given-names>S</given-names>
            </name>
            <name>
              <surname>Whitney</surname>
              <given-names>E</given-names>
            </name>
            <name>
              <surname>Shapiro</surname>
              <given-names>DR</given-names>
            </name>
            <name>
              <surname>Beere</surname>
              <given-names>PA</given-names>
            </name>
          </person-group>
        </element-citation>
      </ref>
      <ref id="B24">
        <mixed-citation>24. The Scandinavian Simvastatin Survival Study Group. Randomised trial of cholesterol lowering in 4,444 patients with coronary heart disease: the Scandinavian Simvatatin Survival Study (4S). Lancet. 1994; 344: 1383-9.</mixed-citation>
        <element-citation publication-type="journal">
          <article-title>Randomised trial of cholesterol lowering in 4,444 patients with coronary heart disease: the Scandinavian Simvatatin Survival Study (4S)</article-title>
          <source>Lancet</source>
          <date>
            <year>1994</year>
          </date>
          <fpage>1383</fpage>
          <lpage>9</lpage>
          <volume>344</volume>
        </element-citation>
      </ref>
      <ref id="B25">
        <mixed-citation>25. Shepherd J, Blauw GJ, Murphy MB. Pravastatin in elderly individuals at risk of vascular disease (PROSPER): a randomised controlled trial. PROspective Study of Pravastatin in the Elderly at Risk. Lancet. 2002; 360: 1623-30.</mixed-citation>
        <element-citation publication-type="journal">
          <article-title>Pravastatin in elderly individuals at risk of vascular disease (PROSPER): a randomised controlled trial. PROspective Study of Pravastatin in the Elderly at Risk</article-title>
          <source>Lancet</source>
          <date>
            <year>2002</year>
          </date>
          <fpage>1623</fpage>
          <lpage>30</lpage>
          <volume>360</volume>
          <person-group person-group-type="author">
            <name>
              <surname>Shepherd</surname>
              <given-names>J</given-names>
            </name>
            <name>
              <surname>Blauw</surname>
              <given-names>GJ</given-names>
            </name>
            <name>
              <surname>Murphy</surname>
              <given-names>MB</given-names>
            </name>
          </person-group>
        </element-citation>
      </ref>
      <ref id="B26">
        <mixed-citation>26. MRC/BHF heart protection study of cholesterol lowering with sinvastatin in 20536 high-risk individuals: a randomised placebo-controlled trial. Lancet. 2002; 360: 7-22.</mixed-citation>
        <element-citation publication-type="journal">
          <article-title>MRC/BHF heart protection study of cholesterol lowering with sinvastatin in 20536 high-risk individuals: a randomised placebo-controlled trial</article-title>
          <source>Lancet</source>
          <date>
            <year>2002</year>
          </date>
          <fpage>7</fpage>
          <lpage>22</lpage>
          <volume>360</volume>
        </element-citation>
      </ref>
      <ref id="B27">
        <mixed-citation>27. Grundy SM. Slide Atlas of lipid disorders. 3<sup>rd</sup>. ed. New York: Gower Medical Publishing; 1990.</mixed-citation>
        <element-citation publication-type="book">
          <source>Slide Atlas of lipid disorders</source>
          <date>
            <year>1990</year>
          </date>
          <person-group person-group-type="author">
            <name>
              <surname>Grundy</surname>
              <given-names>SM</given-names>
            </name>
          </person-group>
        </element-citation>
      </ref>
      <ref id="B28">
        <mixed-citation>28. Kannel WB, Wilson PW, Nam BH, D'Agostino RB. Risk stratification of obesity as a coronary risk factor. Am J Cardiol. 2002; 90: 697-701.</mixed-citation>
        <element-citation publication-type="journal">
          <article-title>Risk stratification of obesity as a coronary risk factor</article-title>
          <source>Am J Cardiol</source>
          <date>
            <year>2002</year>
          </date>
          <fpage>697</fpage>
          <lpage>701</lpage>
          <volume>90</volume>
          <person-group person-group-type="author">
            <name>
              <surname>Kannel</surname>
              <given-names>WB</given-names>
            </name>
            <name>
              <surname>Wilson</surname>
              <given-names>PW</given-names>
            </name>
            <name>
              <surname>Nam</surname>
              <given-names>BH</given-names>
            </name>
            <name>
              <surname>D'Agostino</surname>
              <given-names>RB</given-names>
            </name>
          </person-group>
        </element-citation>
      </ref>
      <ref id="B29">
        <mixed-citation>29. Scott M, Grundy SM. Obesity, metabolic syndrome, and coronary atherosclerosis. Circulation. 2002; 105 (23): 2696-8.</mixed-citation>
        <element-citation publication-type="journal">
          <article-title>Obesity, metabolic syndrome, and coronary atherosclerosis</article-title>
          <source>Circulation</source>
          <date>
            <year>2002</year>
          </date>
          <fpage>2696</fpage>
          <lpage>8</lpage>
          <issue>23</issue>
          <volume>105</volume>
          <person-group person-group-type="author">
            <name>
              <surname>Scott</surname>
              <given-names>M</given-names>
            </name>
            <name>
              <surname>Grundy</surname>
              <given-names>SM</given-names>
            </name>
          </person-group>
        </element-citation>
      </ref>
      <ref id="B30">
        <mixed-citation>30. Krause MV, Mahan LK. (eds.). Alimentos, nutri&#231;&#227;o e dietoterapia. 10&#350; ed. S&#227;o Paulo: Roca; 2002.</mixed-citation>
        <element-citation publication-type="book">
          <source>Alimentos, nutri&#231;&#227;o e dietoterapia</source>
          <date>
            <year>2002</year>
          </date>
          <person-group person-group-type="author">
            <name>
              <surname>Krause</surname>
              <given-names>MV</given-names>
            </name>
            <name>
              <surname>Mahan</surname>
              <given-names>LK</given-names>
            </name>
          </person-group>
        </element-citation>
      </ref>
      <ref id="B31">
        <mixed-citation>31. Davies MJ, Judd JT, Baer DJ, Clevidence BA, Paul DR, Edwards AJ, et al. Black tea consumption reduces total and LDL cholesterol in mildly hypercholesterolemic adults. J Nutr. 2003; 133: 3298S-3302S.</mixed-citation>
        <element-citation publication-type="journal">
          <article-title>Black tea consumption reduces total and LDL cholesterol in mildly hypercholesterolemic adults</article-title>
          <source>J Nutr</source>
          <date>
            <year>2003</year>
          </date>
          <fpage>3298S</fpage>
          <lpage>3302S</lpage>
          <volume>133</volume>
          <person-group person-group-type="author">
            <name>
              <surname>Davies</surname>
              <given-names>MJ</given-names>
            </name>
            <name>
              <surname>Judd</surname>
              <given-names>JT</given-names>
            </name>
            <name>
              <surname>Baer</surname>
              <given-names>DJ</given-names>
            </name>
            <name>
              <surname>Clevidence</surname>
              <given-names>BA</given-names>
            </name>
            <name>
              <surname>Paul</surname>
              <given-names>DR</given-names>
            </name>
            <name>
              <surname>Edwards</surname>
              <given-names>AJ</given-names>
            </name>
          </person-group>
        </element-citation>
      </ref>
      <ref id="B32">
        <mixed-citation>32. Kajimoto O, Kajimoto Y, Yabune M, Nozawa A, Nagata K, Kakuda T. Tea catechins reduce serum cholesterol levels in mild borderline hypercholesterolemic patients. J Clin Biochem Nutr. 2003; 33: 101-11.</mixed-citation>
        <element-citation publication-type="journal">
          <article-title>Tea catechins reduce serum cholesterol levels in mild borderline hypercholesterolemic patients</article-title>
          <source>J Clin Biochem Nutr</source>
          <date>
            <year>2003</year>
          </date>
          <fpage>101</fpage>
          <lpage>11</lpage>
          <volume>33</volume>
          <person-group person-group-type="author">
            <name>
              <surname>Kajimoto</surname>
              <given-names>O</given-names>
            </name>
            <name>
              <surname>Kajimoto</surname>
              <given-names>Y</given-names>
            </name>
            <name>
              <surname>Yabune</surname>
              <given-names>M</given-names>
            </name>
            <name>
              <surname>Nozawa</surname>
              <given-names>A</given-names>
            </name>
            <name>
              <surname>Nagata</surname>
              <given-names>K</given-names>
            </name>
            <name>
              <surname>Kakuda</surname>
              <given-names>T</given-names>
            </name>
          </person-group>
        </element-citation>
      </ref>
      <ref id="B33">
        <mixed-citation>33. Kajimoto O, Kajimoto Y, Yabune M, Nakamura T, Kotani K, Suzuki Y, et al. Tea catechins with a galloyl moiety reduce body weight and fat. J Health Sci. 2005; 51: 161-71.</mixed-citation>
        <element-citation publication-type="journal">
          <article-title>Tea catechins with a galloyl moiety reduce body weight and fat</article-title>
          <source>J Health Sci</source>
          <date>
            <year>2005</year>
          </date>
          <fpage>161</fpage>
          <lpage>71</lpage>
          <volume>51</volume>
          <person-group person-group-type="author">
            <name>
              <surname>Kajimoto</surname>
              <given-names>O</given-names>
            </name>
            <name>
              <surname>Kajimoto</surname>
              <given-names>Y</given-names>
            </name>
            <name>
              <surname>Yabune</surname>
              <given-names>M</given-names>
            </name>
            <name>
              <surname>Nakamura</surname>
              <given-names>T</given-names>
            </name>
            <name>
              <surname>Kotani</surname>
              <given-names>K</given-names>
            </name>
            <name>
              <surname>Suzuki</surname>
              <given-names>Y</given-names>
            </name>
          </person-group>
        </element-citation>
      </ref>
      <ref id="B34">
        <mixed-citation>34. Geleijnse JM, Launer LJ, Van der Kuip DA, Hofman A, Witteman JC. Inverse association of tea and flavonoid intakes with incident myocardial infarction: the Rotterdam Study. Am J Clin Nutr. 2002; 75 (5): 880-6.</mixed-citation>
        <element-citation publication-type="journal">
          <article-title>Inverse association of tea and flavonoid intakes with incident myocardial infarction: the Rotterdam Study</article-title>
          <source>Am J Clin Nutr</source>
          <date>
            <year>2002</year>
          </date>
          <fpage>880</fpage>
          <lpage>6</lpage>
          <issue>5</issue>
          <volume>75</volume>
          <person-group person-group-type="author">
            <name>
              <surname>Geleijnse</surname>
              <given-names>JM</given-names>
            </name>
            <name>
              <surname>Launer</surname>
              <given-names>LJ</given-names>
            </name>
          </person-group>
        </element-citation>
      </ref>
      <ref id="B35">
        <mixed-citation>35. Dulloo AG, Duret C, Rohrer D, Girardier L, Mensi N, Fathi M, et al. Efficacy of a green tea extract rich in catechin polyphenols and caffeine in increasing 24-h energy expenditure and fat oxidation in humans. Am J Clin Nutr. 1999; 70: 1040-5.</mixed-citation>
        <element-citation publication-type="journal">
          <article-title>Efficacy of a green tea extract rich in catechin polyphenols and caffeine in increasing 24-h energy expenditure and fat oxidation in humans</article-title>
          <source>Am J Clin Nutr</source>
          <date>
            <year>1999</year>
          </date>
          <fpage>1040</fpage>
          <lpage>5</lpage>
          <volume>70</volume>
          <person-group person-group-type="author">
            <name>
              <surname>Dulloo</surname>
              <given-names>AG</given-names>
            </name>
            <name>
              <surname>Duret</surname>
              <given-names>C</given-names>
            </name>
            <name>
              <surname>Rohrer</surname>
              <given-names>D</given-names>
            </name>
            <name>
              <surname>Girardier</surname>
              <given-names>L</given-names>
            </name>
            <name>
              <surname>Mensi</surname>
              <given-names>N</given-names>
            </name>
            <name>
              <surname>Fathi</surname>
              <given-names>M</given-names>
            </name>
          </person-group>
        </element-citation>
      </ref>
      <ref id="B36">
        <mixed-citation>36. Chantre P, Lairon D. Recent findings of green tea extract AR25 (Exolise) and its activity for the treatment of obesity. <bold>Phytomedicine. 2002; 9 (1): 3-8.</bold></mixed-citation>
        <element-citation publication-type="journal">
          <article-title>Recent findings of green tea extract AR25 (Exolise) and its activity for the treatment of obesity</article-title>
          <source>Phytomedicine</source>
          <date>
            <year>2002</year>
          </date>
          <fpage>3</fpage>
          <lpage>8</lpage>
          <issue>1</issue>
          <volume>9</volume>
          <person-group person-group-type="author">
            <name>
              <surname>Chantre</surname>
              <given-names>P</given-names>
            </name>
            <name>
              <surname>Lairon</surname>
              <given-names>D</given-names>
            </name>
          </person-group>
        </element-citation>
      </ref>
    </ref-list>
  </back>
  <sub-article article-type="translation" id="TRen" xml:lang="en">
    <front-stub>
      <article-categories>
        <subj-group subj-group-type="heading">
          <subject>Original Articles</subject>
        </subj-group>
      </article-categories>
      <title-group>
        <article-title xml:lang="en">Prospective double-blind crossover study of Camellia sinensis (green tea) in dyslipidemias</article-title>
      </title-group>
      <abstract xml:lang="en">
        <p>BACKGROUND: Epidemiological studies have established an association between dyslipidemias and atherosclerosis. Nutritional therapy is a key point in the prevention strategy for individuals who present with risk factors for atherosclerotic disease. OBJECTIVES: To investigate the effects of green tea (Camellia sinensis) in patients with dyslipidemias. METHODS: The study included 33 patients aged between 21 and 71 years who had a low-fat diet (25-35% of total calories and 200 mg of cholesterol per day). They were randomized for two sequential treatments: 250-mg capsules of green tea dry extract or placebo for a total period of 16 weeks; each patient received green tea (Camellia sinensis) for eight weeks and placebo for another eight weeks. RESULTS: Baseline lipid values (mg/dL) were: HDL-cholesterol 60.7 &#177; 7.3; total cholesterol 255 &#177; 30.9; LDL-cholesterol 158.8 &#177; 29.0; triglycerides 169.0 &#177; 61.3 and Apo-B 120.2 &#177; 18.9. Mean lipid variations induced by the use of green tea (Camellia sinensis) showed a 3.9% reduction (p = 0.006) in total cholesterol concentrations and a 4.5% reduction (p = 0.026) in LDL-cholesterol. The intake of green tea did not significantly influence HDL-cholesterol, triglyceride, and Apo-B levels. Non-significant results were found in the assessment of blood lipids (total cholesterol and LDL-cholesterol) with the use of placebo. CONCLUSION: A beneficial effect of green tea (Camellia sinensis) was demonstrated, with a significant reduction of total cholesterol and LDL-cholesterol levels in eight weeks, in the patients studied.</p>
      </abstract>
      <kwd-group xml:lang="en">
        <kwd>Epidemiologic studies</kwd>
        <kwd>case-control studies</kwd>
        <kwd>thea sinensis</kwd>
        <kwd>Camellia sinensis</kwd>
        <kwd>phytotherapy</kwd>
        <kwd>dyslipidemias</kwd>
      </kwd-group>
    </front-stub>
    <body>
      <p>
        <bold>ORIGINAL ARTICLE</bold>
      </p>
      <p>Prospective double-blind crossover study of <italic><bold>Camellia sinensis </bold></italic>(green tea) in dyslipidemias</p>
      <p>
        <bold>Gesiani de Almeida Pierin Batista; Cl&#225;udio L. Pereira da Cunha; Maril&#233;ia Scartezini; Raul von der Heyde; Mur&#237;lo G Bitencourt; Sandra Fabr&#237;cio de Melo </bold>
      </p>
      <p>Universidade Federal do Paran&#225;, PR - Brasil</p>
      <p>
        <xref ref-type="corresp" rid="cor-body2">Mailing address</xref>
      </p>
      <p>
        <bold>SUMMARY</bold>
      </p>
      <p><bold>BACKGROUND:</bold> Epidemiological studies have established an association between dyslipidemias and atherosclerosis. Nutritional therapy is a key point in the prevention strategy for individuals who present with risk factors for atherosclerotic disease.</p>
      <p><bold>OBJECTIVES:</bold> To investigate the effects of green tea <italic>(Camellia sinensis)</italic> in patients with dyslipidemias.</p>
      <p><bold>METHODS:</bold> The study included 33 patients aged between 21 and 71 years who had a low-fat diet (25-35% of total calories and 200 mg of cholesterol per day). They were randomized for two sequential treatments: 250 mg capsules of green tea dry extract or placebo for a total period of 16 weeks; each patient received green tea <italic>(Camellia sinensis)</italic> for eight weeks and placebo for another eight weeks.</p>
      <p><bold>RESULTS:</bold> Baseline lipid values (mg/dL) were: HDL-cholesterol 60.7 &#177; 7.3; total cholesterol 255 &#177; 30.9; LDL-cholesterol 158.8 &#177; 29.0; triglycerides 169.0 &#177; 61.3 and Apo-B 120.2 &#177; 18.9. Mean lipid variations induced by the use of green tea <italic>(Camellia sinensis)</italic> showed a 3.9% reduction (p = 0.006) in total cholesterol concentrations and a 4.5% reduction (p = 0.026) in LDL-cholesterol. The intake of green tea did not significantly influence HDL-cholesterol, triglyceride, and Apo-B levels. Non-significant results were found in the assessment of blood lipids (total cholesterol and LDL-cholesterol) with the use of placebo.</p>
      <p><bold>CONCLUSION:</bold> A beneficial effect of green tea <italic>(Camellia sinensis)</italic> was demonstrated, with a significant reduction of total cholesterol and LDL-cholesterol levels in eight weeks, in the patients studied.</p>
      <p><bold>Key words:</bold> Epidemiologic studies; case-control studies; thea sinensis; <italic>Camellia sinensis</italic>; phytotherapy; dyslipidemias.</p>
      <p>
        <bold>Introduction</bold>
      </p>
      <p>Green tea (<italic>Camellia sinensis</italic>) is one of the oldest beverages in the world. Reports on the habit of drinking tea date back to ancient times, when plants were used as medicines both in the prevention and the treatment of disorders, dysfunctions or diseases in humans and other animals<sup>1-3</sup>. In the past years, growing attention has been given to the use of green tea in human health promotion. Reduction of blood levels of total cholesterol and LDL-cholesterol with the use of this tea has been repeatedly demonstrated in several studies<sup>4-6</sup>. The green tea compounds responsible for these changes have not yet been determined. Recently, some studies have postulated that, thanks to their high concentration of antioxidant polyphenols, green tea flavonoids (catechins), especially epigallocatekin gallate (EGCG), may be responsible for the beneficial effects of green tea<sup>7-12</sup>. Tea flavonoids are believed to be effective antioxidants that can protect against several chronic diseases, especially cardiovascular diseases. Based on the observation that the consumption of flavonoid-rich food contributes to a cardiovascular risk reduction, the objective of this study design was to evaluate green tea as a diet component and its relation with blood lipid profiles in the primary prevention treatment of patients with dyslipidemias. </p>
      <p>Green tea originated in southern China and is cultivated in Asia and in Central African countries. It has been consumed for more than 3,000 years in China, which is its major producer. In Japan, it started to be consumed by Buddhist monks in the 9th century a.D.<sup>13 </sup>Tea extract is a water-soluble product obtained by infusion. The three major types of tea are black, oolong and green tea. Non-fermented green tea is produced from fresh leaves of <italic>Camellia sinensis</italic>, a plant that contains water, protein, carbohydrates, minerals, vitamins, and flavonoid-like polyphenols. The major green tea flavonoids are the catechins epigallocatechin gallate (EGCG), which comprise one third of its total dry weight. Green tea is weakly aromatic; its taste is bitter, and the infusion is green. It is also known as Thea sinensis. Black tea is fully fermented. Its manufacturing includes an enzymatic oxidation in which most of the catechins (polyphenols) are converted into complex condensation products (theaflavins / thearubigins). Oloong tea is semi-fermented and elaborated mainly in China and Taiwan<sup>14</sup>.</p>
      <p>
        <bold>Methods</bold>
      </p>
      <p>This study was conducted in the Dyslipidemia Outpatient Service of <italic>Hospital das Cl&#237;nicas da Universidade Federal do Paran&#225; (UFPR)</italic>. A total of 38 hypercholesterolemic patients aged between 21 and 71 years participated in the study. The research was approved by the Ethics Committee on Human Research of <italic>Hospital de Cl&#237;nicas da UFPR</italic>, and a written informed consent was obtained from all participants. </p>
      <p>
        <bold>Patient selection</bold>
      </p>
      <p>The following criteria were used for patient inclusion in the study: men and women older than 20 years of age, with no evidence of coronary artery disease, with total cholesterol (TC) &gt; 200 mg/ml and LDL-cholesterol &gt; 130 mg/dl. Patients with renal or hepatic failure, hypothyroidism and diabetes were excluded from the study. All participants included in the study underwent clinical examination and nutritional assessment. Blood pressure was measured using the palpatory and auscultatory methods with a mercury sphygmomanometer, according to instructions of the V Brazilian Guidelines on Hypertension<sup>15</sup>, 2006.</p>
      <p>
        <bold>Assessments</bold>
      </p>
      <p>For the nutritional assessment, conventional methods such as anthropometry, clinical, family and diet history were used. Weight, height, body mass index (BMI), body composition using bioelectrical impedance analysis (BIA) and waist circumference were assessed. Eating habits were assessed by means of food frequency, 24-hour dietary recalls, and three-day dietary records. Based on these data, customized nutrition prescriptions were elaborated for all patients, and were monthly monitored for a 16-week period. </p>
      <p>
        <bold>Diet design</bold>
      </p>
      <p>The diet prescription consisted of an intake of less than 35% of the total kilocalories from total fat, with less than 7% of saturated fat, 10% or less of polyunsaturated fat, and up to 20% of monounsaturated fat. The amount of cholesterol recommended was less than 200 mg/day, in conformity with the guidelines of the III National Cholesterol Education Program - NCEP<sup>16</sup>. All patients followed this baseline diet for 16 weeks, during which they were randomized to receive one of the treatments, including daily doses of capsules containing 250 mg of dry green tea extract (<italic>Camellia sinensis</italic>) or placebo every eight weeks. Because this was a double-blind crossover study, both the participants and the researchers were not aware of the sequence in which the substances would be administered. After eight weeks of treatment, the order was inverted: the group which was receiving green tea would now start to receive placebo and vice-versa for eight more weeks. The patients were also advised not to use any vitamin supplement during the investigation period. They were also informed of the importance of diet compliance and of the need for a change in lifestyle (weight control, physical activity, smoking and alcohol cessation). Levels of lipids, total cholesterol, HDL-cholesterol, LDL-cholesterol, triglycerides and apolipoprotein B (Apo-B), as well as of lifestyle changes were monitored. </p>
      <p>
        <bold>Evaluation of data</bold>
      </p>
      <p>The patients had their lipid profile determined after a 12 to 14-hour period of fasting. Serum levels of triglyceride and cholesterol fractions were quantified using the homogeneous colorimetric enzymatic method; LDL-cholesterol was estimated by the Friedewald formula<sup>17</sup>, and apolipoprotein B (Apo-B) was determined using the Dade Behring kit. The Bayer alkaline picrate method was used for glucose determination, and an ion-selective electrode was used for sodium and potassium determination.</p>
      <p>Data were expressed as mean &#177; standard deviation of the mean. The parametric paired Student's t test and the non-parametric paired-sample Wilcoxon test were used to test the variables (by means of the Primer of Biostatistics software). The level of significance (significance probability) was set at lower than 5% (p&lt;0.05).</p>
      <p>
        <bold>Results</bold>
      </p>
      <p>
        <bold>Demographic data</bold>
      </p>
      <p>A total of 33 patients participated in the study. The predominant level of regular education was elementary school, with family income between one and two minimum wages. Most of the patients were women (84.8%); 15.2% were men. The mean age of the patients was 55.4 &#177; 10.1 years (ranging from 21 to 71 years). Anthropometric characteristics of the study group are shown in <xref ref-type="table" rid="tab1-body2">Table 1</xref>.</p>
      <table-wrap id="tab1-body2">
        <graphic xlink:href="1678-4170-abc-93-02-0128-00010-gt01-en.jpg"/></table-wrap>
      <p>In relation to the anthropometric parameters, weight change was observed in the overall assessment of the group. In the pre-green tea period (71.4 &#177; 15.8 kg) and in the post-tea period (70.2 &#177; 15.4 kg), a 1.7% (p=0.002) weight loss and 1.7% (p=0.002) BMI reduction were observed while the patients were using green tea. In comparison with the pre-placebo (70.6 &#177; 15.5 kg) and post-placebo (69.9 &#177; 14.9) periods, there was also weight loss although with a lower statistical significance: the weight loss was of 1.1% (p=0.041) and BMI reduction of 1.1% (p=0.047). Data regarding systolic and diastolic blood pressures showed no significant changes. </p>
      <p>During the eight weeks when capsules containing dry green tea extracts (250 mg) were administered, we observed a significant change in blood lipid levels, especially a plasma LDL-c reduction. The assessment of the lipid profile (<xref ref-type="table" rid="en_a10tab02-body2">Table 2</xref>) pre and post-tea and pre and post-placebo showed that with tea intake there was a reduction in total cholesterol (3.9%) (p=0.006) and in LDL (4.5%) (p=0.026). A non-significant reduction in HDL (2.1%) (p=0.218) and non-significant increase in TG (7.5%) (p=0.807) and Apo-B (4.4%) (p=0.180) were also observed. With placebo, there was a non-significant reduction in total cholesterol (2.6%) (p=0.168), LDL (1.8%) (p=0.396), HDL (4.2%) (p=0.080) and Apo-B (0.8%) (p=0.677), and a non-significant increase in TG (1.9%) (p=0.733). </p>
      <p content-type="asset">
        <table-wrap id="en_a10tab02-body2">
          <graphic xlink:href="1678-4170-abc-93-02-0128-00010-gt02-en.jpg"/></table-wrap>
      </p>
      <p>As regards the effects of diet intervention, after 16 weeks of treatment the nutritional needs were adequate to the recommendations and the eating changes obtained when under diet had an influence on the consumption of fats, especially on a significant reduction of saturated fatty acids. These values are shown in <xref ref-type="table" rid="en_a10tab03-body2">Table 3</xref>.</p>
      <p content-type="asset">
        <table-wrap id="en_a10tab03-body2">
          <graphic xlink:href="1678-4170-abc-93-02-0128-00010-gt03-en.jpg"/></table-wrap>
      </p>
      <p>
        <bold>Discussion</bold>
      </p>
      <p>Dyslipidemias are among the major risk factors for atherosclerotic cardiovascular diseases. Several studies have shown that the fight against dyslipidemias brings benefits to patients at different cardiovascular risks, and that by reducing hypercholesterolemia increasingly more beneficial effects on the reduction of coronary events are provided<sup>17-27</sup>. With these studies, significant advances were obtained concerning the knowledge and control of dyslipidemias. </p>
      <p>The treatment program recommended for dyslipidemias is based on blood lipid level monitoring and on the adoption of interventions on lifestyle, which include healthy eating habits, maintenance of the ideal weight, regular physical activity, and fight against cigarette smoking. Diet intervention is the first approach in the treatment of dyslipidemias, and should be maintained even when drug therapy is required<sup>28-30</sup>.</p>
      <p>The American Heart Association stresses the use of a diet including a variety of fruits, vegetables and grains, because these foods may reduce the risk of cardiovascular diseases by providing the vitamins, antioxidant nutrients (flavonoids), phytochemicals and fibers they contain<sup>16</sup>. </p>
      <p>In the present study, with the diet intervention adopted we could evaluate the effects of green tea together with a diet following the recommendations of the American Heart Association and of the National Program of Education on Cholesterol<sup>30</sup>, without the interference from the variation of other diet nutrients or components. </p>
      <p>In order to include green tea in the diet as a double-blind intervention, we could not introduce it as a beverage, because of the difficulty in monitoring its preparation and the amount ingested. Thus, it was necessary to administer it in the form of capsules, in an amount equivalent to four tea cups (150mL) per day.</p>
      <p>In this study, after the interventions, the mean lipid changes induced by the use of green tea (<italic>Camellia sinensis</italic>) showed a reduction by 3.9% (p=0.006) in total cholesterol concentrations and a reduction by 4.5% (p=0.026) in LDL-cholesterol. This amount of green tea consumed did not significantly influence the levels of HDL-c, triglycerides and Apo-B. The absence of a significant change in Apo-B, which did not follow the LDL-c reduction, was particularly noteworthy. We believe that this can be explained by the small number of patients and the short follow-up period; this difference could not be observed with a sample of this size. From the biochemical point of view, a hypothesis to justify the absence of a significant change in Apo-B levels could be the fact that the Apo-B percentage in low-density lipoproteins is lower than that of LDL-cholesterol, so the change was not significant in this small sample. No significant differences were found in lipid levels with the use of placebo.</p>
      <p>Although this study included a relatively small number of volunteers, our results corroborate those of the first clinical experiment in humans conducted by Maron et al in 2003<sup>13</sup>, which assessed 240 hospitalized individuals with dyslipidemias in China. The researchers demonstrated in a double-blind, placebo-controlled study that the patients who had taken capsules containing tea extract for 12 weeks showed a reduction by 11.3% in total cholesterol levels and by 16% in LDL-cholesterol levels.</p>
      <p>In another study similar to ours, Davies et al<sup>31</sup> assessed the effect of green tea on 15 adult volunteers with mild hypercholesterolemia, who also received a step I-type diet, as described by the American Heart Association and by the National Cholesterol Education Program. After three weeks of treatment, the investigators found that five cups of tea per day reduced total cholesterol by 6.5% and LDL-cholesterol by 11.1% in comparison to placebo beverages. These findings were similar to those verified in our study.</p>
      <p>In another double-blind study conducted in 2003, Kajimoto et al<sup>32</sup> showed that treatment with an intake of 395 mg/day of green tea significantly reduced total cholesterol levels after eight weeks of treatment in patients with moderate hypercholesterolemia: this was not observed in the placebo group. More recently, in a study with a different design also conducted by Kajimoto<sup>33</sup>, the treatment with higher tea doses (666 mg/day) produced additional reductions in total cholesterol in comparison to the group consuming 444 mg/day, but both groups showed significant reductions in total cholesterol and LDL-cholesterol. </p>
      <p>In Tokunga et al's study<sup>4</sup> conducted in 2002 with 13,916 Japanese individuals, green tea consumption was associated with a reduction in serum cholesterol levels when the total intake was higher than 10 cups per day. However, when correlated with lifestyle aspects of the population (smoking, use of coffee and alcohol), BMI and age, reduction in cholesterol had already been observed with the ingestion of only one cup of tea per day.</p>
      <p>Other studies showed the beneficial effect of tea on reducing the incidence of cardiovascular diseases<sup>32,34</sup>.</p>
      <p>Although our results showed that green tea intake as part of the diet contributed to a reduction in blood lipids, it was not possible to evaluate the mechanisms through which flavonoids produce this effect. However, this was not the objective of our research.</p>
      <p>Also, another benefit attributed to tea consumption was related to the anthropometric parameters: weight loss by 1.7% (p=0.002) and BMI reduction by 1.7% (p=0.002) were observed. In the placebo group, the variation was significant, although smaller: weight loss by 1.1% (p=0.041) and BMI reduction by 1.1% (p=0.047). </p>
      <p>Weight control is an important factor especially in patients with cardiovascular risks. Two important studies evaluated the thermogenic effect of tea in humans. In 1999, Dulloo et al<sup>35</sup> reported the effect of green tea extract containing caffeine and polyphenols, showing an increased 24-hour energy expenditure and fat oxidation in healthy young people. An equivalent dose of caffeine did not produce the same effect, and the researchers suggested that tea polyphenols were accountable for that effect.</p>
      <p>In another study, Chantre and Lairon<sup>36</sup> also demonstrated that green tea caused weight loss and attributed this effect to increased thermogenesis. After a 3-month intervention, a reduction of waist circumference by 4.48% and of weight by 4.6% was observed.</p>
      <p>Regarding the other diet components, after 16 weeks of treatment, the nutritional requirements were adequate to the NCEP - ATP III recommendations<sup>15</sup>. Eating changes obtained with diet had an influence on fat consumption, especially regarding the reduction of saturated fatty acids. There was a very significant reduction of total calorie intake (p=0.0001), reduction in the consumption of total fat, saturated fat, and cholesterol (p=0.0001), and increase in fiber consumption (p=0.0001). We also observed increased protein consumption (p=0.0001). These changes could be explained by the restriction in fatty foods (beef and derivatives, trans fat and fried food in general), which were replaced by other sources including the group of milk and skim milk products, as well as soy protein.</p>
      <p>The potential of flavonoids in the prevention of cardiovascular diseases has become increasingly clearer. Their biologically active substances have a reductant effect on LDL-cholesterol, comparable to or greater than that obtained with low saturated fat and cholesterol diets. Although there are no randomized clinical trials demonstrating that these vegetable substances reduce cardiovascular morbidity and mortality, it is believed that these foods could be regularly included in a cardioprotective diet.</p>
      <p>
        <bold>Conclusion</bold>
      </p>
      <p>These findings show benefits of green tea (<italic>Camellia Sinensis</italic>), in concordance with previous studies of the literature. However, further investigations with a greater number of patients and longer follow-up periods are necessary to validate our initial observations.</p>
      <p>
        <bold>Potential Conflict of Interest</bold>
      </p>
      <p>No potential conflict of interest relevant to this article was reported.</p>
      <p>
        <bold>Sources of Funding</bold>
      </p>
      <p>This study was funded by Universidade Federal do Paran&#225; and partially funded by Laborat&#243;rio de Manipula&#231;&#227;o Bio Store.</p>
      <p>
        <bold>Study Association</bold>
      </p>
      <p>This article is part of the thesis of master submitted by Gesiani de Almeida Pierin Batista, from Universidade Federal do Paran&#225;.</p>
      <p>
        <bold>References</bold>
      </p>
      <p content-type="ref-to-delete">1. Korolkovas A. A riqueza potencial de nossa flora. Rev Bras Farmacognosia. 1996; 1: 1-7. </p>
      <p content-type="ref-to-delete">2. Rates SMK. Plants as source of drugs. Toxicon. 2001; 39: 603-13. </p>
      <p content-type="ref-to-delete">3. Maron DJ, Sibilo GL, Sheng CN, Swu ZG, Li YH, Chen H, et al. Cholesterol-lowering effect of a theaflavin-enriched green tea extract: a randomized controlled trial. Arch Intern Med. 2003; 163: 1448-53. </p>
      <p content-type="ref-to-delete">4. Tokunaga S, White IR, Frost C, Tanaka K, Kono S. Green tea consumption and serum lipids and lipoproteins in a population of healthy workers in Japan. Ann Epidemiol. 2002; 12: 157-65.  </p>
      <p content-type="ref-to-delete">5. Hertog MG, Kromhout D, Aravanis C, Blackburn H, Buzina R, Fidanza F, et al. Flavonoid intake and long-term risk of coronary heart disease and cancer in the seven countries study. Arch Intern Med. 1995; 155 (4): 381-6.  </p>
      <p content-type="ref-to-delete">6. Mukamal KJ, Maclure M, Muller JE. Tea consumption and mortality after acute myocardial infarction. Circulation. 2002; 105: 2476-81. </p>
      <p content-type="ref-to-delete">7. Hodgson JM, Puddey IB, Croft KD. Acute effects of ingestion of black and green tea on lipoprotein oxidation. Am J Clin Nutr. 2000; 71 (5): 1103-7. </p>
      <p content-type="ref-to-delete">8. Leung LK, Su RCY, Zesheng Z, Huang Y, Chen ZY. Theaflavins in black and catechins in green tea are equally effective antioxidants. J Nutr. 2001; 131: 2248-51. </p>
      <p content-type="ref-to-delete">9. Hodgson JM, Croft KD, Mori TA, Burke V, Beilin LJ, Puddley IB. Regular ingestion of tea does not inhibit in vivo lipid peroxidation in humans. J Nutr. 2002; 132: 55-8. </p>
      <p content-type="ref-to-delete">10. Duffy SJ, Vita JA, Holbrook M, Swerdloff PL, Keaney JF Jr. Effect of acute and chronic tea consumption on platelet aggregation in patients with coronary artery disease. Arterioscler Thromb Vasc Biol. 2001; 21 (6): 1084-9. </p>
      <p content-type="ref-to-delete">11. Simin L, Manson JAE, Lee IM, Cole SR, Hennekens CH, Willett WC, et al. Fruit and vegetable intake and risk of cardiovascular disease: the Women's Health Study. Am J Clin Nutr. 2000; 72: 922-8. </p>
      <p content-type="ref-to-delete">12. Siddiqui IA, Afaq F, Adhami VM, Ahmad N, Mukhtar H. Antioxidants of the beverage tea in promotion of human health. Antioxid Redox Signal. 2004; 6 (3): 571-82. </p>
      <p content-type="ref-to-delete">13. Chopra D. The Chopra Center Herbal Handbook. USA: Three Rivers Press; 2000. </p>
      <p content-type="ref-to-delete">14. Ody P. The Herb Society's complete medicinal herbal. London: Dorling Kindersley; 1993. </p>
      <p content-type="ref-to-delete">15. Sociedade Brasileira de Cardiologia. Sociedade Brasileira de Hipertens&#227;o. V Diretrizes Brasileiras de Hipertens&#227;o arterial. 2006. (on line). [acesso em 2007 setembro 10]. Dispon&#237;vel em: <ext-link ext-link-type="uri" xlink:href="http://publicacoes.cardiol.br/consenso/2006/VDiretriz-HA.pdf">http://publicacoes.cardiol.br/consenso/2006/VDiretriz-HA.pdf</ext-link> </p>
      <p content-type="ref-to-delete">16. Third Report of the National Cholesterol Education Program (NCEP). Expert panel on detection, evaluation, and treatment of high blood cholesterol in adults (Adult Treatment Panel III) National Cholesterol Education Program (NCEP). Expert panel on Detection, Evaluation and Treatment of High Blood Cholesterol in adults. Circulation. 2002; 106 (25): 3143-421. </p>
      <p content-type="ref-to-delete">17. Santos RD, Sp&#243;sito AC, Santos JE, Fonseca FH, Moriguchi EH, Martinez TLR, et al. Programa de avalia&#231;&#227;o nacional do conhecimento sobre preven&#231;&#227;o da aterosclerose (PANDORA): como tem sido feito o tratamento das dislipidemias pelos m&#233;dicos brasileiros. Arq Bras Cardiol. 2000; 75: 289-95. </p>
      <p content-type="ref-to-delete">18. Santos Filho RD, Martinez TLR. Fatores de risco para doen&#231;a cardiovascular: velhos e novos fatores de risco, velhos problemas! Arq Bras Endocrinol Metab. 2002; 46 (3): 212-4. </p>
      <p content-type="ref-to-delete">19. Castelli WP. Cholesterol and lipids in the risk of coronary artery disease: the Framingham Heart Study. Can J Cardiol. 1998; 4 (Suppl A): 5A-10A. </p>
      <p content-type="ref-to-delete">20. Server PS, Dahlof B, Poulter NR, Wedel H, Beevers G, Caulfield M, et al. Prevention of coronary and stroke events with atorvastatin in hypertensive patients who have average or lower-than-average cholesterol concentrations, in the Anglo-Scandinavian Cardiac Outcomes Trial - Lipid Lowering Arm (ASCOT-LLA): a multicentre randomised controlled trial. Lancet. 2003; 361: 1149-58. </p>
      <p content-type="ref-to-delete">21. Kannel WB, Castelli WP, Gordon T. Serum cholesterol lipoproteins and of coronary heart disease: the Framinghan study. Ann Int Med. 1971; 74: 1-12. </p>
      <p content-type="ref-to-delete">22. Assmann G, Schulte H. Results and conclusions of the Prospective Cardiovascular Munster (PROCAM) Study. In: Assmann G. (ed). Lipid metabolism disorders and coronary heart disease. 2<sup>nd. </sup>ed. Stuttgart: FK Schattauer; 1993.  </p>
      <p content-type="ref-to-delete">23. Downs JR, Clearfield M, Weis S, Whitney E, Shapiro DR, Beere PA, et al. For the AFCAPS/TexCAPS Research Group. Primary prevention of acute coronary events with lovastatin in men and women with average cholesterol levels: results of AFCAPS/TexCAPS. JAMA. 1998; 279: 1615-22. </p>
      <p content-type="ref-to-delete">24. The Scandinavian Simvastatin Survival Study Group. Randomised trial of cholesterol lowering in 4,444 patients with coronary heart disease: the Scandinavian Simvatatin Survival Study (4S). Lancet. 1994; 344: 1383-9. </p>
      <p content-type="ref-to-delete">25. Shepherd J, Blauw GJ, Murphy MB. Pravastatin in elderly individuals at risk of vascular disease (PROSPER): a randomised controlled trial. PROspective Study of Pravastatin in the Elderly at Risk. Lancet. 2002; 360: 1623-30. </p>
      <p content-type="ref-to-delete">26. MRC/BHF heart protection study of cholesterol lowering with sinvastatin in 20536 high-risk individuals: a randomised placebo-controlled trial. Lancet. 2002; 360: 7-22.  </p>
      <p content-type="ref-to-delete">27. Grundy SM. Slide Atlas of lipid disorders. 3<sup>rd</sup>. ed. New York: Gower Medical Publishing; 1990.  </p>
      <p content-type="ref-to-delete">28. Kannel WB, Wilson PW, Nam BH, D'Agostino RB. Risk stratification of obesity as a coronary risk factor. Am J Cardiol. 2002; 90: 697-701. </p>
      <p content-type="ref-to-delete">29. Scott M, Grundy SM. Obesity, metabolic syndrome, and coronary atherosclerosis. Circulation. 2002; 105 (23): 2696-8. </p>
      <p content-type="ref-to-delete">30. Krause MV, Mahan LK. (eds.). Alimentos, nutri&#231;&#227;o e dietoterapia. 10&#170; ed. S&#227;o Paulo: Roca; 2002. </p>
      <p content-type="ref-to-delete">31. Davies MJ, Judd JT, Baer DJ, Clevidence BA, Paul DR, Edwards AJ, et al. Black tea consumption reduces total and LDL cholesterol in mildly hypercholesterolemic adults. J Nutr. 2003; 133: 3298S-3302S.  </p>
      <p content-type="ref-to-delete">32. Kajimoto O, Kajimoto Y, Yabune M, Nozawa A, Nagata K, Kakuda T. Tea catechins reduce serum cholesterol levels in mild borderline hypercholesterolemic patients. J Clin Biochem Nutr. 2003; 33: 101-11. </p>
      <p content-type="ref-to-delete">33. Kajimoto O, Kajimoto Y, Yabune M, Nakamura T, Kotani K, Suzuki Y, et al. Tea catechins with a galloyl moiety reduce body weight and fat. J Health Sci. 2005; 51: 161-71. </p>
      <p content-type="ref-to-delete">34. Geleijnse JM, Launer LJ, Van der Kuip DA, Hofman A, Witteman JC. Inverse association of tea and flavonoid intakes with incident myocardial infarction: the Rotterdam Study. Am J Clin Nutr. 2002; 75 (5): 880-6.  </p>
      <p content-type="ref-to-delete">35. Dulloo AG, Duret C, Rohrer D, Girardier L, Mensi N, Fathi M, et al. Efficacy of a green tea extract rich in catechin polyphenols and caffeine in increasing 24-h energy expenditure and fat oxidation in humans. Am J Clin Nutr. 1999; 70: 1040-5. </p>
      <p>36. Chantre P, Lairon D. Recent findings of green tea extract AR25 (Exolise) and its activity for the treatment of obesity. <bold>Phytomedicine. 2002; 9 (1): 3-8.  </bold>    </p>
      <p>
        <fn id="cor-body2" fn-type="corresp">
          <p>Mailing address:</p>
          <p> Gesiani de Almeida Pierin Batista </p>
          <p> Rua Bar&#227;o do Rio Branco, 2013 / 02 - Centro </p>
          <p> 83750-000, Lapa, PR - Brazil</p>
          <p> Email: </p>
          <p>
            <email xlink:href="gesiani@uol.com.br">gesiani@uol.com.br</email>
          </p>
        </fn>
      </p>
      <p>Manuscript received August 21, 2008; revised manuscript received October 22, 2008; accepted November 14, 2008.</p>
    </body>
  </sub-article>
  <sub-article article-type="translation" id="TRes" xml:lang="es">
    <front-stub>
      <article-categories/>
      <title-group>
        <article-title xml:lang="es">Estudio prospectivo, doble ciego y cruzado de la Camellia sinensis (t&#233; verde) en las dislipidemias</article-title>
      </title-group>
      <abstract xml:lang="es">
        <p>FUNDAMENTO: Estudios epidemiol&#243;gicos establecieron una asociaci&#243;n entre dislipidemias y aterosclerosis. La terapia nutricional es un punto central de la estrategia preventiva en individuos que presentan factores de riesgo para enfermedad ateroscler&#243;tica. OBJETIVO: Investigar los efectos del t&#233; verde (Camellia sinensis) en pacientes portadores de dislipidemias. M&#201;TODOS: El estudio implic&#243; a 33 pacientes, con edad entre 21 y 71 a&#241;os, que consum&#237;an una dieta con bajo tenor graso (el 25% al 35% de las calor&#237;as totales y 200mg de colesterol por d&#237;a). Se randomizaron para dos tratamientos secuenciales: c&#225;psulas conteniendo 250mg de extracto seco del t&#233; verde o placebo, administradas por un per&#237;odo total de 16 semanas, habiendo cada paciente utilizado t&#233; verde (Camellia sinensis) por ocho semanas y placebo en igual per&#237;odo. RESULTADOS: Los valores lip&#237;dicos basales (mg/dl) fueron los siguientes: HDL-colesterol 60,7 &#177; 7,3; colesterol total 255 &#177; 30,9; LDL-colesterol 158,8 &#177; 29,0; triglic&#233;ridos 169,0 &#177; 61,3 y Apo-B 120,2 &#177; 18,9. Las variaciones lip&#237;dicas promedios, provocadas por el uso del t&#233; verde (Camellia sinensis), evidenciaron una reducci&#243;n de un 3,9 % (p = 0,006) en las concentraciones del colesterol total y una reducci&#243;n de un 4,5 % (p = 0,026) del LDL-colesterol. La ingesti&#243;n de t&#233; verde no influenci&#243; significativamente los niveles de HDL-colesterol, de los triglic&#233;ridos y de la Apo-B. Resultados no significativos se observaron en la evaluaci&#243;n de los l&#237;pidos sangu&#237;neos (colesterol total y LDL-colesterol) con el empleo del placebo. CONCLUSI&#211;N: Se evidenci&#243; el efecto ben&#233;fico del t&#233; verde (Camellia sinensis), que redujo significativamente, en ocho semanas, los niveles de colesterol total y LDL-colesterol en ese grupo de pacientes.</p>
      </abstract>
      <kwd-group xml:lang="es">
        <kwd>Estudios epidemiol&#243;gicos</kwd>
        <kwd>estudios de casos y controles</kwd>
        <kwd>t&#233; verde</kwd>
        <kwd>Camellia sinensis</kwd>
        <kwd>fitoterapia</kwd>
        <kwd>dislipidemias</kwd>
      </kwd-group>
    </front-stub>
    <body>
      <p>
        <bold>ART&#205;CULO ORIGINAL</bold>
      </p>
      <p>Estudio prospectivo, doble ciego y cruzado de la <italic><bold>Camellia Sinensis</bold></italic> (t&#233; verde) en las dislipidemias</p>
      <p>
        <bold>Gesiani de Almeida Pierin Batista; Cl&#225;udio L. Pereira da Cunha; Maril&#233;ia Scartezini; Raul von der Heyde; Mur&#237;lo G Bitencourt; Sandra Fabr&#237;cio de Melo</bold>
      </p>
      <p>Universidade Federal do Paran&#225;, PR - Brasil</p>
      <p>
        <xref ref-type="corresp" rid="end-body3">Correspondencia</xref>
      </p>
      <p>
        <bold>RESUMEN</bold>
      </p>
      <p><bold>FUNDAMENTO:</bold> Estudios epidemiol&#243;gicos establecieron una asociaci&#243;n entre dislipidemias y aterosclerosis. La terapia nutricional es un punto central de la estrategia preventiva en individuos que presentan factores de riesgo para enfermedad ateroscler&#243;tica.</p>
      <p><bold>OBJETIVOS:</bold> Investigar los efectos del t&#233; verde (<italic>Camellia sinensis</italic>) en pacientes portadores de dislipidemias.</p>
      <p><bold>M&#201;TODOS:</bold> El estudio implic&#243; a 33 pacientes, con edad entre 21 y 71 a&#241;os, que consum&#237;an una dieta con bajo tenor graso (el 25% al 35% de las calor&#237;as totales y 200mg de colesterol por d&#237;a). Se randomizaron para dos tratamientos secuenciales: c&#225;psulas conteniendo 250mg de extracto seco del t&#233; verde o placebo, administradas por un per&#237;odo total de 16 semanas, habiendo cada paciente utilizado t&#233; verde (<italic>Camellia sinensis</italic>) por ocho semanas y placebo en igual per&#237;odo.</p>
      <p><bold>RESULTADOS:</bold> Los valores lip&#237;dicos basales (mg/dl) fueron los siguientes: HDL-colesterol 60,7 &#177; 7,3; colesterol total 255 &#177; 30,9; LDL-colesterol 158,8 &#177; 29,0; triglic&#233;ridos 169,0 &#177; 61,3 y Apo-B 120,2 &#177; 18,9. Las variaciones lip&#237;dicas promedios, provocadas por el uso del t&#233; verde (<italic>Camellia sinensis</italic>), evidenciaron una reducci&#243;n de un 3,9 % (p = 0,006) en las concentraciones del colesterol total y una reducci&#243;n de un 4,5 % (p = 0,026) del LDL-colesterol. La ingesti&#243;n de t&#233; verde no influenci&#243; significativamente los niveles de HDL-colesterol, de los triglic&#233;ridos y de la Apo-B. Resultados no significativos se observaron en la evaluaci&#243;n de los l&#237;pidos sangu&#237;neos (colesterol total y LDL-colesterol) con el empleo del placebo.</p>
      <p><bold>CONCLUSI&#211;N:</bold> Se evidenci&#243; el efecto ben&#233;fico del t&#233; verde (<italic>Camellia sinensis</italic>), que redujo significativamente, en ocho semanas, los niveles de colesterol total y LDL-colesterol en ese grupo de pacientes. (Arq Bras Cardiol 2009; 93(2) : 125-131)</p>
      <p><bold>Palabras clave:</bold> Estudios epidemiol&#243;gicos, estudios de casos y controles, t&#233; verde, <italic>Camellia sinensis</italic>, fitoterapia, dislipidemias.</p>
      <p>
        <bold>Introducci&#243;n</bold>
      </p>
      <p>El t&#233; verde (<italic>Camellia sinensis</italic>) es una de las bebidas m&#225;s antiguas del mundo. El h&#225;bito de consumir el t&#233; es referido desde la antig&#252;edad, cuando se utilizaban las plantas como medicamentos, tanto en la prevenci&#243;n como en el tratamiento de disturbios, disfunciones o enfermedades en seres humanos y animales<sup>1-3</sup>. En los &#250;ltimos a&#241;os, se ha prestado creciente atenci&#243;n al uso del t&#233; verde en la promoci&#243;n de la salud humana. La reducci&#243;n en las concentraciones sangu&#237;neas del colesterol total y del LDL-colesterol, por medio del consumo de ese t&#233;, ha sido repetidamente demostrada en diversos estudios<sup>4-6</sup>. Sin embargo, los componentes del t&#233; verde responsables de esas alteraciones todav&#237;a no est&#225;n bien aclarados. Recientemente, algunos estudios postularon que los flavonoides del t&#233; verde (catequinas), sobre todo la epigalocatequina gallate (EGCG), debido a su alta concentraci&#243;n de polifenoles antioxidantes, puedan ser responsables de la acci&#243;n ben&#233;fica<sup>7-12</sup> del t&#233;. Se cree a&#250;n que los flavonoides del t&#233; sean efectivos antioxidantes y puedan proteger el organismo contra diversas enfermedades cr&#243;nicas, principalmente las enfermedades cardiovasculares. Desde la observaci&#243;n que el consumo de alimentos ricos en flavonoides contribuye a la reducci&#243;n del riesgo cardiovascular, el dibujo de este estudio tuvo por objetivo evaluar el t&#233; verde como componente de la dieta, adem&#225;s de su relaci&#243;n sobre los perfiles lip&#237;dicos sangu&#237;neos en el tratamiento de prevenci&#243;n primaria en pacientes portadores de dislipidemias.</p>
      <p>El t&#233; verde tiene su origen en la regi&#243;n sur de China y se lo cultiva en Asia y en los pa&#237;ses de &#193;frica Central. En China, se consume el t&#233; desde hace miles de a&#241;os, siendo ese pa&#237;s su principal productor. En Jap&#243;n, su consumo empez&#243; por medio de los monjes budistas en los a&#241;os 800 d.C.<sup>13</sup>. El extracto de t&#233; es un producto soluble en agua obtenido por infusi&#243;n. Los tres principales tipos de t&#233; son el negro, el oolong y el verde. El t&#233; verde, no fermentado, se produce a partir de las hojas frescas de la planta <italic>Camellia sinensis</italic>, que contiene: agua, prote&#237;nas, hidratos de carbono, minerales, vitaminas y polifenoles del tipo flavonoides. Los principales flavonoides del t&#233; verde son las catequinas epigalocatequina gallate (EGCG), las que constituyen un tercio 1/3 del peso seco total. Ese t&#233; es poco arom&#225;tico, tiene sabor amargo y la infusi&#243;n obtenida es verdosa. Se lo conoce tambi&#233;n como Thea sinensis. Sin embargo, el t&#233; negro, t&#233; de fermentaci&#243;n completa, incluye en su manufactura una oxidaci&#243;n enzim&#225;tica, en la que la mayor&#237;a de las catequinas (polifenoles) se convierte en productos de condensaci&#243;n complejos (teaflavinas, tearubigina). E por fin, el t&#233; oolong es semifermentado y elaborado principalmente en China y Taiwan<sup>14</sup>.</p>
      <p>
        <bold>M&#233;todos</bold>
      </p>
      <p>Este estudio se condujo en el ambulatorio de Dislipidemias del Hospital de Cl&#237;nicas de la Universidad Federal del Paran&#225; (UFPR). Participaron 38 pacientes portadores de hipercolesterolemia, con edades entre 21 y 71 a&#241;os. El Comit&#233; de &#201;tica en Investigaci&#243;n en Seres Humanos del Hospital de Cl&#237;nicas de la UFPR aprob&#243; la investigaci&#243;n, y el formulario de consentimiento informado de todos los participantes.</p>
      <p>
        <bold>Selecci&#243;n de los pacientes</bold>
      </p>
      <p>Los criterios utilizados para la inclusi&#243;n de los pacientes en el estudio fueron: varones y mujeres con edad superior a 20 a&#241;os, sin evidencia de enfermedad coronaria, con colesterol total (CT) &gt; 200mg/dl y LDL-colesterol superior a 130mg/dl. Excluimos del estudio los pacientes portadores de insuficiencia renal o hep&#225;tica, hipotireoidismo y diabetes. Todos los participantes incluidos en el estudio fueron sometidos al examen cl&#237;nico y la evaluaci&#243;n nutricional. La toma de la presi&#243;n arterial se llev&#243; a cabo por los m&#233;todos palpatorio y ausculatorio, con empleo de esfigmoman&#243;metro de columna de mercurio, siguiendo las orientaciones de las V Directrices Brasile&#241;as de Hipertensi&#243;n Arterial<sup>15</sup>, en el 2006.</p>
      <p>
        <bold>Evaluaciones</bold>
      </p>
      <p>En la evaluaci&#243;n nutricional utilizamos los m&#233;todos convencionales como la antropometr&#237;a y el hist&#243;rico cl&#237;nico, familiar y diet&#233;tico. Evaluamos el peso, la estatura, el &#237;ndice de masa corporal (IMC), la composici&#243;n corporal, por medio de bioimpedancia el&#233;ctrica (BIA), y la circunferencia abdominal. Los h&#225;bitos alimentarios se evaluaron por medio de la frecuencia de los alimentos, recordatorio alimentario de 24h y registro alimentario de tres d&#237;as. Con base en esos datos, se elaboraron las orientaciones nutricionales individualizadas para todos los pacientes, monitoreadas mensualmente durante un per&#237;odo de 16 semanas.</p>
      <p>
        <bold>Dise&#241;o de la dieta</bold>
      </p>
      <p>La prescripci&#243;n diet&#233;tica consisti&#243; en la ingesta menor que el 35% del total de kilocalor&#237;as en la forma de l&#237;pidos totales, con menos del 7% de grasa saturada, cantidad igual o inferior al 10% de grasa poliinsaturada, y hasta el 20% de grasa monoiinsaturada. La cantidad de colesterol recomendada fue menos de 200 mg/d&#237;a, en conformidad con las orientaciones del III National Cholesterol Education Program (NCEP)<sup>16</sup>. Todos los pacientes siguieron esa dieta basal durante 16 semanas, per&#237;odo por el que se randomizaron para recibir uno de los tratamientos, incluyendo dosis diarias de c&#225;psulas conteniendo 250mg de extracto seco del t&#233; verde (<italic>Camellia sinensis</italic>) o placebo, a cada ocho semanas. Por tratarse de un estudio cruzado y doble ciego, tanto los participantes, como los investigadores, no sab&#237;an el orden en que las substancias se administrar&#237;an. Tras ocho semanas de tratamiento, hubo una inversi&#243;n de los procedimientos: el grupo que recib&#237;a el t&#233; verde pas&#243; a recibir el placebo y viceversa, por ocho semanas m&#225;s. Los pacientes tambi&#233;n fueron orientados a no utilizar cualesquier suplementos vitam&#237;nicos durante el per&#237;odo de investigaci&#243;n. Todav&#237;a se les informaron sobre la importancia de la adhesi&#243;n a la dieta y de la necesidad del cambio en el estilo de vida (control del peso, actividad f&#237;sica, abstinencia de fumo y alcohol). Hubo monitoreo de los niveles lip&#237;dicos, del colesterol total, del HDL-colesterol, del LDL-colesterol, de los triglic&#233;ridos, de la apolipoprote&#237;na B (Apo-B) y de los cambios en el estilo de vida.</p>
      <p>
        <bold>Evaluaci&#243;n de los datos</bold>
      </p>
      <p>Los pacientes tuvieron su perfil lip&#237;dico determinado tras ayuno alimentario de 12 a 14 horas. Los valores s&#233;ricos de los triglic&#233;ridos y del colesterol fraccionado se cuantificaron mediante el m&#233;todo colorim&#233;trico enzim&#225;tico homog&#233;neo; el LDL-colesterol se estim&#243; con la f&#243;rmula de Friedewald<sup>17</sup> y, para la dosificaci&#243;n de la apolipoprote&#237;na B (Apo-B), se utiliz&#243; el kit Dade. Con la ayuda del m&#233;todo Picrate Alcaline Bayer se dosific&#243; la glucosa, y los valores de sodio y potasio obtenidos por electrodos iones selectivos.</p>
      <p>Los datos se expresaron en promedio &#177; error est&#225;ndar del promedio. Para la comprobaci&#243;n de las variables, se utilizaron las siguientes pruebas: la prueba param&#233;trica t de Sudent para muestras emparejadas y la no-param&#233;trica Wilcoxon para muestras emparejadas (por medio del software Primer of Biostatistics). El nivel de significancia (probabilidad de significancia) adoptado fue menor que el 5% (p&lt;0,05).</p>
      <p>
        <bold>Resultados</bold>
      </p>
      <p>
        <bold>Datos demogr&#225;ficos</bold>
      </p>
      <p>En el total, 33 pacientes concluyeron el estudio. El nivel de escolaridad predominante era de ense&#241;anza fundamental, con renta familiar entre uno y dos salarios m&#237;nimos. El total de un 84,8% de los pacientes era del sexo femenino, contra un 15,2% del sexo masculino. La edad promedio de los pacientes era de 55,4 &#177; 10,1 a&#241;os (variando entre 21 y 71 a&#241;os). Las caracter&#237;sticas antropom&#233;tricas del grupo estudiado est&#225;n relacionadas en la <xref ref-type="table" rid="tab1-body3">Tabla 1</xref>.</p>
      <table-wrap id="tab1-body3">
        <graphic xlink:href="1678-4170-abc-93-02-0128-00010-gt01-es.jpg"/></table-wrap>
      <p>Con relaci&#243;n a los par&#225;metros antropom&#233;tricos, hubo variaci&#243;n de peso en la evaluaci&#243;n general del grupo. En el per&#237;odo pre t&#233; (71,4&#177;15,8kg) y post t&#233; (70,2&#177;15,4kg), se observ&#243; la p&#233;rdida de peso en un 1,7% (p=0,002) y la disminuci&#243;n del IMC en un 1,7% (p=0,002) mientras que los pacientes usaban el t&#233; verde. Comparado al per&#237;odo pre placebo (70,6+-15,5kg) y post placebo (69,9+-14,9), tambi&#233;n hubo p&#233;rdida ponderal con significancia estad&#237;stica menos expresiva; la p&#233;rdida de peso fue de un 1,1% (p=0,041) y la reducci&#243;n del IMC de un 1,1% (p=0,047). Los datos de las presiones arteriales sist&#243;lica y diast&#243;lica no sufrieron alteraciones significativas.</p>
      <p>Al administrarse durante ocho semanas c&#225;psulas conteniendo extracto seco de t&#233; verde (250mg), observamos una variaci&#243;n significativa en los niveles de l&#237;pidos sangu&#237;neos, principalmente en la reducci&#243;n de la LDL-c en el plasma. En la evaluaci&#243;n del perfil lip&#237;dico (ver <xref ref-type="table" rid="es_a10tab02-body3">Tabla 2</xref>), en cuanto a las situaciones pre y post t&#233; y pre y post placebo, se observ&#243; que: con la ingesta de t&#233; hubo la reducci&#243;n del colesterol total (3,9%) (p=0,006) y la reducci&#243;n del LDL (4,5%) (p=0,026). Tambi&#233;n se nota la disminuci&#243;n no significativa del HDL (2,1%) (p=0,218) y el aumento no significativo de los TG (7,5%) (p=0,807) y del APO-B (4,4%) (p=0,180). Con el placebo hubo la disminuci&#243;n no significativa del colesterol total (2,6%) (p=0,168), del LDL (1,8%) (p=0,396), del HDL (4,2%) (p=0,080) y de la APO-B (0,8%) (p=0,677), adem&#225;s del aumento no significativo del TG (1,9%) (p=0,733).</p>
      <p content-type="asset">
        <table-wrap id="es_a10tab02-body3">
          <graphic xlink:href="1678-4170-abc-93-02-0128-00010-gt02-es.jpg"/></table-wrap>
      </p>
      <p>Respecto a los efectos de la intervenci&#243;n diet&#233;tica, tras 16 semanas de tratamiento, las necesidades diet&#233;ticas estaban adecuadas a las recomendaciones y los cambios alimentarios, obtenidos por medio de la dieta, tuvieron influencia sobre el consumo de grasas, principalmente en la reducci&#243;n significativa de los &#225;cidos grasos saturados. Los valores est&#225;n presentados en la <xref ref-type="table" rid="es_a10tab03-body3">Tabla 3</xref>.</p>
      <p content-type="asset">
        <table-wrap id="es_a10tab03-body3">
          <graphic xlink:href="1678-4170-abc-93-02-0128-00010-gt03-es.jpg"/></table-wrap>
      </p>
      <p>
        <bold>Discusi&#243;n</bold>
      </p>
      <p>Las dislipidemias est&#225;n entre los m&#225;s importantes factores de riesgo de la enfermedad cardiovascular ateroscler&#243;tica. Diversos estudios han evidenciado que el combate a las dislipidemias trae beneficios a pacientes en diferentes riesgos cardiovasculares. Adem&#225;s, a trav&#233;s de las reducciones de las hipercolesterolemias, se proporcionan efectos ben&#233;ficos cada vez mayores en la reducci&#243;n de eventos coronarios<sup>17-27</sup>. De esos estudios, se lograron avances significativos en el conocimiento y control de las dislipidemias.</p>
      <p>El programa de tratamiento recomendado para las dislipidemias toma como base el monitoreo de los niveles de los l&#237;pidos sangu&#237;neos y en la instituci&#243;n de intervenciones en el estilo de vida. Esas intervenciones comprenden h&#225;bitos alimentarios sanos, el mantenimiento del peso ideal, la actividad f&#237;sica regular y el combate al tabaquismo. La intervenci&#243;n diet&#233;tica es el primer abordaje en el tratamiento de dislipidemias, que debe mantenerse aun ante la necesidad de intervenci&#243;n medicamentosa<sup>28-30</sup>.</p>
      <p>La <italic>American Heart Association (AHA)</italic> enfatiza el uso de una dieta que incluya una variedad de frutas, vegetales y granos, ya que esos alimentos pueden reducir el riesgo de enfermedades cardiovasculares, por medio de la oferta de vitaminas, nutrientes antioxidantes (flavonoides), fitoqu&#237;micos y fibras en ellos contenidos<sup>16</sup>.</p>
      <p>En el presente estudio, la intervenci&#243;n diet&#233;tica adoptada permiti&#243; a nosotros evaluar los efectos del t&#233; verde junto a una dieta adecuada a las recomendaciones de la AHA y del Programa Nacional de Educaci&#243;n en Colesterol<sup>30</sup>, libre de la interferencia por la variaci&#243;n de otros nutrientes o componentes de la dieta.</p>
      <p>Con el prop&#243;sito de incluir el t&#233; verde en la dieta como intervenci&#243;n doble ciega, no fue posible introducirlo como bebida, debido a la dificultad de monitorear la forma de preparaci&#243;n y la cantidad ingerida, habiendo sido necesario administrarlo en la forma de c&#225;psula, o el equivalente a cuatro tazas de t&#233; (150 ml) por d&#237;a.</p>
      <p>En este estudio, luego de las intervenciones, las variaciones lip&#237;dicas promedios provocadas por el uso del t&#233; verde (<italic>Camellia sinensis</italic>) sufrieron una reducci&#243;n de un 3,9 % (p = 0,006) en las concentraciones de colesterol total y una reducci&#243;n de un 4,5 % (p = 0,026) del LDL - colesterol. Esa cantidad de t&#233; verde ingerida no influenci&#243; significativamente los niveles de HDL-c, de los triglic&#233;ridos y de la Apo-B. Particularmente llam&#243; la atenci&#243;n la ausencia de variaci&#243;n significativa de la Apo-B, que no acompa&#241;&#243; la reducci&#243;n de la LDL-c. Se cree que esto se debe por el n&#250;mero reducido de pacientes en corto per&#237;odo de observaci&#243;n, no sendo posible observar esa diferencia con una muestra de ese tama&#241;o. Desde el punto de vista bioqu&#237;mico, podr&#237;a tenerse como hip&#243;tesis para justificar la ausencia de variaci&#243;n significativa de la Apo-B, el hecho del porcentaje de Apo-B en las lipoprote&#237;nas de baja densidad ser menor que el porcentaje de LDL-colesterol y, en esa muestra peque&#241;a, la variaci&#243;n no fue expresiva. Bajo el uso del placebo, los niveles lip&#237;dicos no presentaron diferencias significativas.</p>
      <p>A pesar de este estudio implicar un n&#250;mero relativamente peque&#241;o de voluntarios, nuestros resultados est&#225;n de acuerdo con la primera experimentaci&#243;n cl&#237;nica en humanos, conducida por Maron et al. En el 2003<sup>13</sup>, que evalu&#243; a 240 personas con dislipidemias internadas en hospitales de China. Los investigadores revelaron, por medio de un estudio doble ciego, con placebo controlado, que los pacientes que hab&#237;an tomado c&#225;psulas conteniendo el extracto de t&#233; por 12 semanas, presentaron una reducci&#243;n de un 11,3% de las tasas del colesterol total y el 16% de las tasas del LDL-colesterol.</p>
      <p>En otro estudio similar a este, Davies et al.<sup>31</sup> evaluaron el efecto del t&#233; verde en 15 voluntarios adultos, con moderada hipercolesterolemia, conjuntamente a la adopci&#243;n de una dieta del tipo etapa I, como descrito por la American Heart Association y por el Programa Nacional de Instrucci&#243;n del Colesterol. Tras tres semanas de tratamiento, los investigadores concluyeron que cinco vasos de t&#233; por d&#237;a redujeron el colesterol total en un 6,5% y la LDL-colesterol en un 11,1%, en comparaci&#243;n a las bebidas del placebo. Esos hallazgos fueron semejantes a los identificados en nuestro estudio.</p>
      <p>En otro estudio, realizado en el 2003, Kajimoto et al.<sup>32</sup>, por medio de un experimento doble ciego, mostraron que el tratamiento con la ingesta de 395 mg/d&#237;a del t&#233; verde redujo significativamente los niveles de colesterol total, tras ocho semanas de administraci&#243;n en pacientes con hipercolesterolemia moderada, lo que no se observ&#243; en el grupo del placebo. M&#225;s recientemente, en otro dise&#241;o, conducido por Kajimoto<sup>33</sup>, el tratamiento con dosis m&#225;s elevadas del t&#233; (666 mg/d&#237;a) produjo una disminuci&#243;n adicional en el colesterol total en comparaci&#243;n al grupo que consum&#237;a 444 mg/d&#237;a, a pesar de ambos los grupos demostrar disminuciones significativas en el colesterol total y en el LDL-colesterol.</p>
      <p>En el estudio realizado por Tokunaga et al. En el 2002<sup>4</sup>, con 13.916 individuos japoneses, el consumo de t&#233; verde fue asociado a la reducci&#243;n de los niveles s&#233;ricos de colesterol, cuando ese consumo exced&#237;a m&#225;s de 10 tazas por d&#237;a. Sin embargo, cuando se relacionaba con los aspectos de estilo de vida de la poblaci&#243;n (tabaquismo, uso de caf&#233; y alcohol), IMC y edad, la reducci&#243;n del colesterol ya se observ&#243; con la ingesta de solamente una taza de t&#233; al d&#237;a. Diversos otros estudios tambi&#233;n evidenciaron el efecto ben&#233;fico del t&#233; en la reducci&#243;n de las enfermedades cardiovasculares<sup>32,34</sup>.</p>
      <p>Aunque nuestros resultados revelen que el consumo de t&#233; verde en la dieta contribuy&#243; a la reducci&#243;n de las grasas sangu&#237;neas, no fue posible evaluar los mecanismos por los cuales los flavonoides producen tal efecto, no siendo ese, no obstante, el objetivo de esta investigaci&#243;n.</p>
      <p>Adem&#225;s de eso, otro beneficio atribuido al consumo del t&#233; verde se identific&#243; respecto a los par&#225;metros antropom&#233;tricos: se observ&#243; p&#233;rdida de peso de un 1,7 % (p=0,002) y disminuci&#243;n del IMC de un 1,7 % (p=0,002). En el grupo placebo, la variaci&#243;n fue significativa sin embargo de menor intensidad, la p&#233;rdida de peso fue del 1,1% (p=0,041) y el IMC tuvo una reducci&#243;n de un 1,1% (p=0,047).</p>
      <p>El control del peso es un factor importante, principalmente en pacientes con riesgos cardiovasculares. Dos estudios importantes han evaluado el efecto termog&#233;nico del t&#233; en seres humanos. En 1999, Dulloo et al.<sup>35</sup> relataron el efecto del extracto de t&#233; verde conteniendo cafe&#237;na y polifenoles, en el aumento del gasto energ&#233;tico de 24 horas y en la oxidaci&#243;n de grasa en j&#243;venes sanos. Una dosis equivalente de cafe&#237;na no provoc&#243; igual efecto, y los investigadores sugirieron que los polifenoles del t&#233; fueron los responsables del resultado.</p>
      <p>En otro estudio, Chantre y Lairon<sup>36</sup> tambi&#233;n revelaron que el t&#233; verde provoc&#243; adelgazamiento y atribuyeron este efecto al aumento de la termog&#233;nesis. Luego de tres meses de intervenci&#243;n, los autores observaron que hubo una reducci&#243;n de un 4,48% en la circunferencia abdominal y de un 4,6% en la reducci&#243;n del peso.</p>
      <p>Respecto a los otros componentes de la dieta, tras 16 semanas de tratamiento, las necesidades diet&#233;ticas estaban adecuadas a las recomendaciones del NCRP - ATP<sup>16</sup><sub>.</sub> Los cambios alimentarios, obtenidos por medio de la dieta, tuvieron influencia sobre el consumo de grasas, principalmente en la reducci&#243;n significativa de los &#225;cidos grasos saturados. Hubo una disminuci&#243;n bastante significativa de la ingesta del valor cal&#243;rico total (p=0,0001), la disminuci&#243;n del consumo de grasas totales, de grasas saturadas y del colesterol (p=0,0001) y el aumento del consumo de fibras (p=0,0001). Evidenciamos tambi&#233;n un aumento en el consumo de prote&#237;nas (p=0,0001). Una explicaci&#243;n para eso puede ser la restricci&#243;n de alimentos grasosos (carne bovina y sus derivados, grasas trans y frituras en general), siendo los mismos sustituidos por otras fuentes, incluyendo el grupo de la leche y sus derivados desnatados, as&#237; como el uso de la prote&#237;na de soja.</p>
      <p>Se vuelve cada vez m&#225;s claro el potencial de los flavonoides en la prevenci&#243;n de las enfermedades cardiovasculares. Sus sustancias biol&#243;gicamente activas tienen efecto reductor sobre el colesterol LDL, comparable o mayor que el logrado con dietas bajas en grasas saturadas y colesterol. A pesar de no haber demostraciones por ensayos cl&#237;nicos randomizados de que esas substancias de origen vegetal reduzcan la morbimortalidad cardiovascular, se cree que esos alimentos puedan formar parte regular de una alimentaci&#243;n cardioprotectora.</p>
      <p>
        <bold>Conclusi&#243;n</bold>
      </p>
      <p>Esos hallazgos muestran los beneficios del t&#233; verde (<italic>Camellia sinensis</italic>), en concordancia con estudios previos de la literatura. Sin embargo revelan tambi&#233;n que a&#250;n son necesarias nuevas investigaciones, con mayor n&#250;mero de pacientes y per&#237;odos de observaci&#243;n m&#225;s largos, para validar las observaciones iniciales realizadas en este estudio.</p>
      <p>
        <bold>Potencial Conflicto de Intereses</bold>
      </p>
      <p>Declaro no haber conflicto de intereses pertinentes.</p>
      <p>
        <bold>Fuentes de Financiaci&#243;n</bold>
      </p>
      <p>La Universidad Federal del Paran&#225; financi&#243; el presente estudio y el Laboratorio de Manipulaci&#243;n Bio Store financi&#243; parcialmente esta investigaci&#243;n.</p>
      <p>
        <bold>Vinculaci&#243;n Acad&#233;mica</bold>
      </p>
      <p>Este art&#237;culo forma parte de tesis de maestr&#237;a de Gesiani de Almeida Pierin Batista, por la Universidad Federal del Paran&#225;.</p>
      <p>
        <bold>Referencias</bold>
      </p>
      <p content-type="ref-to-delete">1. Korolkovas A. A riqueza potencial de nossa flora. Rev Bras Farmacognosia. 1996; 1: 1-7. </p>
      <p content-type="ref-to-delete">2. Rates SMK. Plants as source of drugs. Toxicon. 2001; 39: 603-13. </p>
      <p content-type="ref-to-delete">3. Maron DJ, Sibilo GL, Sheng CN, Swu ZG, Li YH, Chen H, et al. Cholesterol-lowering effect of a theaflavin-enriched green tea extract: a randomized controlled trial. Arch Intern Med. 2003; 163: 1448-53. </p>
      <p content-type="ref-to-delete">4. Tokunaga S, White IR, Frost C, Tanaka K, Kono S. Green tea consumption and serum lipids and lipoproteins in a population of healthy workers in Japan. Ann Epidemiol. 2002; 12: 157-65.  </p>
      <p content-type="ref-to-delete">5. Hertog MG, Kromhout D, Aravanis C, Blackburn H, Buzina R, Fidanza F, et al. Flavonoid intake and long-term risk of coronary heart disease and cancer in the seven countries study. Arch Intern Med. 1995; 155 (4): 381-6.  </p>
      <p content-type="ref-to-delete">6. Mukamal KJ, Maclure M, Muller JE. Tea consumption and mortality after acute myocardial infarction. Circulation. 2002; 105: 2476-81. </p>
      <p content-type="ref-to-delete">7. Hodgson JM, Puddey IB, Croft KD. Acute effects of ingestion of black and green tea on lipoprotein oxidation. Am J Clin Nutr. 2000; 71 (5): 1103-7. </p>
      <p content-type="ref-to-delete">8. Leung LK, Su RCY, Zesheng Z, Huang Y, Chen ZY. Theaflavins in black and catechins in green tea are equally effective antioxidants. J Nutr. 2001; 131: 2248-51. </p>
      <p content-type="ref-to-delete">9. Hodgson JM, Croft KD, Mori TA, Burke V, Beilin LJ, Puddley IB. Regular ingestion of tea does not inhibit in vivo lipid peroxidation in humans. J Nutr. 2002; 132: 55-8. </p>
      <p content-type="ref-to-delete">10. Duffy SJ, Vita JA, Holbrook M, Swerdloff PL, Keaney JF Jr. Effect of acute and chronic tea consumption on platelet aggregation in patients with coronary artery disease. Arterioscler Thromb Vasc Biol. 2001; 21 (6): 1084-9. </p>
      <p content-type="ref-to-delete">11. Simin L, Manson JAE, Lee IM, Cole SR, Hennekens CH, Willett WC, et al. Fruit and vegetable intake and risk of cardiovascular disease: the Women's Health Study. Am J Clin Nutr. 2000; 72: 922-8. </p>
      <p content-type="ref-to-delete">12. Siddiqui IA, Afaq F, Adhami VM, Ahmad N, Mukhtar H. Antioxidants of the beverage tea in promotion of human health. Antioxid Redox Signal. 2004; 6 (3): 571-82. </p>
      <p content-type="ref-to-delete">13. Chopra D. The Chopra Center Herbal Handbook. USA: Three Rivers Press; 2000. </p>
      <p content-type="ref-to-delete">14. Ody P. The Herb Society's complete medicinal herbal. London: Dorling Kindersley; 1993. </p>
      <p content-type="ref-to-delete">15. Sociedade Brasileira de Cardiologia. Sociedade Brasileira de Hipertens&#227;o. V Diretrizes Brasileiras de Hipertens&#227;o arterial. 2006. (on line). [acesso em 2007 setembro 10]. Dispon&#237;vel em: <ext-link ext-link-type="uri" xlink:href="http://publicacoes.cardiol.br/consenso/2006/VDiretriz-HA.pdf">http://publicacoes.cardiol.br/consenso/2006/VDiretriz-HA.pdf</ext-link> </p>
      <p content-type="ref-to-delete">16. Third Report of the National Cholesterol Education Program (NCEP). Expert panel on detection, evaluation, and treatment of high blood cholesterol in adults (Adult Treatment Panel III) National Cholesterol Education Program (NCEP). Expert panel on Detection, Evaluation and Treatment of High Blood Cholesterol in adults. Circulation. 2002; 106 (25): 3143-421. </p>
      <p content-type="ref-to-delete">17. Santos RD, Sp&#243;sito AC, Santos JE, Fonseca FH, Moriguchi EH, Martinez TLR, et al. Programa de avalia&#231;&#227;o nacional do conhecimento sobre preven&#231;&#227;o da aterosclerose (PANDORA): como tem sido feito o tratamento das dislipidemias pelos m&#233;dicos brasileiros. Arq Bras Cardiol. 2000; 75: 289-95. </p>
      <p content-type="ref-to-delete">18. Santos Filho RD, Martinez TLR. Fatores de risco para doen&#231;a cardiovascular: velhos e novos fatores de risco, velhos problemas! Arq Bras Endocrinol Metab. 2002; 46 (3): 212-4. </p>
      <p content-type="ref-to-delete">19. Castelli WP. Cholesterol and lipids in the risk of coronary artery disease: the Framingham Heart Study. Can J Cardiol. 1998; 4 (Suppl A): 5A-10A. </p>
      <p content-type="ref-to-delete">20. Server PS, Dahlof B, Poulter NR, Wedel H, Beevers G, Caulfield M, et al. Prevention of coronary and stroke events with atorvastatin in hypertensive patients who have average or lower-than-average cholesterol concentrations, in the Anglo-Scandinavian Cardiac Outcomes Trial - Lipid Lowering Arm (ASCOT-LLA): a multicentre randomised controlled trial. Lancet. 2003; 361: 1149-58. </p>
      <p content-type="ref-to-delete">21. Kannel WB, Castelli WP, Gordon T. Serum cholesterol lipoproteins and of coronary heart disease: the Framinghan study. Ann Int Med. 1971; 74: 1-12. </p>
      <p content-type="ref-to-delete">22. Assmann G, Schulte H. Results and conclusions of the Prospective Cardiovascular Munster (PROCAM) Study. In: Assmann G. (ed). Lipid metabolism disorders and coronary heart disease. 2<sup>nd. </sup>ed. Stuttgart: FK Schattauer; 1993.  </p>
      <p content-type="ref-to-delete">23. Downs JR, Clearfield M, Weis S, Whitney E, Shapiro DR, Beere PA, et al. For the AFCAPS/TexCAPS Research Group. Primary prevention of acute coronary events with lovastatin in men and women with average cholesterol levels: results of AFCAPS/TexCAPS. JAMA. 1998; 279: 1615-22. </p>
      <p content-type="ref-to-delete">24. The Scandinavian Simvastatin Survival Study Group. Randomised trial of cholesterol lowering in 4,444 patients with coronary heart disease: the Scandinavian Simvatatin Survival Study (4S). Lancet. 1994; 344: 1383-9. </p>
      <p content-type="ref-to-delete">25. Shepherd J, Blauw GJ, Murphy MB. Pravastatin in elderly individuals at risk of vascular disease (PROSPER): a randomised controlled trial. PROspective Study of Pravastatin in the Elderly at Risk. Lancet. 2002; 360: 1623-30. </p>
      <p content-type="ref-to-delete">26. MRC/BHF heart protection study of cholesterol lowering with sinvastatin in 20536 high-risk individuals: a randomised placebo-controlled trial. Lancet. 2002; 360: 7-22.  </p>
      <p content-type="ref-to-delete">27. Grundy SM. Slide Atlas of lipid disorders. 3<sup>rd</sup>. ed. New York: Gower Medical Publishing; 1990.  </p>
      <p content-type="ref-to-delete">28. Kannel WB, Wilson PW, Nam BH, D'Agostino RB. Risk stratification of obesity as a coronary risk factor. Am J Cardiol. 2002; 90: 697-701. </p>
      <p content-type="ref-to-delete">29. Scott M, Grundy SM. Obesity, metabolic syndrome, and coronary atherosclerosis. Circulation. 2002; 105 (23): 2696-8. </p>
      <p content-type="ref-to-delete">30. Krause MV, Mahan LK. (eds.). Alimentos, nutri&#231;&#227;o e dietoterapia. 10&#170; ed. S&#227;o Paulo: Roca; 2002. </p>
      <p content-type="ref-to-delete">31. Davies MJ, Judd JT, Baer DJ, Clevidence BA, Paul DR, Edwards AJ, et al. Black tea consumption reduces total and LDL cholesterol in mildly hypercholesterolemic adults. J Nutr. 2003; 133: 3298S-3302S.  </p>
      <p content-type="ref-to-delete">32. Kajimoto O, Kajimoto Y, Yabune M, Nozawa A, Nagata K, Kakuda T. Tea catechins reduce serum cholesterol levels in mild borderline hypercholesterolemic patients. J Clin Biochem Nutr. 2003; 33: 101-11. </p>
      <p content-type="ref-to-delete">33. Kajimoto O, Kajimoto Y, Yabune M, Nakamura T, Kotani K, Suzuki Y, et al. Tea catechins with a galloyl moiety reduce body weight and fat. J Health Sci. 2005; 51: 161-71. </p>
      <p content-type="ref-to-delete">34. Geleijnse JM, Launer LJ, Van der Kuip DA, Hofman A, Witteman JC. Inverse association of tea and flavonoid intakes with incident myocardial infarction: the Rotterdam Study. Am J Clin Nutr. 2002; 75 (5): 880-6.  </p>
      <p content-type="ref-to-delete">35. Dulloo AG, Duret C, Rohrer D, Girardier L, Mensi N, Fathi M, et al. Efficacy of a green tea extract rich in catechin polyphenols and caffeine in increasing 24-h energy expenditure and fat oxidation in humans. Am J Clin Nutr. 1999; 70: 1040-5. </p>
      <p>36. Chantre P, Lairon D. Recent findings of green tea extract AR25 (Exolise) and its activity for the treatment of obesity. <bold>Phytomedicine. 2002; 9 (1): 3-8.  </bold>    </p>
      <p>
        <fn id="end-body3" fn-type="corresp">
          <p>Correspondencia:</p>
          <p> Gesiani de Almeida Pierin Batista</p>
          <p> Rua Bar&#227;o do Rio Branco, 2013 / 02 - Centro </p>
          <p> 83750-000, Lapa, PR - Brasil</p>
          <p> Email: </p>
          <p>
            <email xlink:href="gesiani@uol.com.br">gesiani@uol.com.br</email>
          </p>
        </fn>
      </p>
      <p>Art&#237;culo recibido el 21/08/08; revisado recibido el 22/10/08; aceptado el 14/11/08.</p>
    </body>
  </sub-article>
</article>
