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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">QfTKSjPLMjQVXKwP4Kk94Ly</article-id>
      <article-id pub-id-type="other">00012</article-id>
      <article-id pub-id-type="publisher-id" specific-use="scielo-v2">S0066-782X2011001200012</article-id>
      <article-id pub-id-type="publisher-id" specific-use="scielo-v1">S0066-782X(11)09700312</article-id>
      <article-id pub-id-type="doi">10.1590/S0066-782X2011001200012</article-id>
      <article-categories>
        <subj-group subj-group-type="heading">
          <subject>Artigo de Revis&#227;o</subject>
        </subj-group>
      </article-categories>
      <title-group>
        <article-title>Interven&#231;&#245;es nutricionais em S&#237;ndrome Metab&#243;lica: uma revis&#227;o sistem&#225;tica</article-title>
      </title-group>
      <contrib-group>
        <contrib contrib-type="author">
          <name>
            <surname>Le&#227;o</surname>
            <given-names>Leila Sicupira Carneiro de Souza</given-names>
          </name>
          <xref ref-type="aff" rid="aff01"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Moraes</surname>
            <given-names>Milena Miranda de</given-names>
          </name>
          <xref ref-type="aff" rid="aff01"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Carvalho</surname>
            <given-names>Giulia Xavier de</given-names>
          </name>
          <xref ref-type="aff" rid="aff01"/>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Koifman</surname>
            <given-names>Rosalina Jorge</given-names>
          </name>
          <xref ref-type="aff" rid="aff01"/>
        </contrib>
      </contrib-group>
      <aff id="aff01">
        <addr-line>
          <named-content content-type="city">Rio de Janeiro</named-content>
          <named-content content-type="state">Rio de Janeiro</named-content>
        </addr-line>
        <institution content-type="orgname">Universidade Federal do Estado do Rio de Janeiro</institution>
        <institution content-type="orgdiv1">FIOCRUZ </institution>
        <institution content-type="orgdiv2">Escola Nacional de Sa&#250;de P&#250;blica</institution>
        <country country="BR">Brazil</country>
      </aff>
      <pub-date date-type="collection" publication-format="electronic">
        <month>09</month>
        <year>2011</year>
      </pub-date>
      <volume>97</volume>
      <issue>3</issue>
      <fpage>260</fpage>
      <lpage>265</lpage>
      <history>
        <date date-type="rev-recd">
          <day>29</day>
          <month>06</month>
          <year>2010</year>
        </date>
        <date date-type="received">
          <day>05</day>
          <month>04</month>
          <year>2010</year>
        </date>
        <date date-type="accepted">
          <day>16</day>
          <month>08</month>
          <year>2010</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>N&#227;o existe consenso sobre a estrat&#233;gia nutricional mais adequada para tratar a S&#237;ndrome Metab&#243;lica (SM), de tal forma que ocorra redu&#231;&#227;o do risco cardiovascular. O presente estudo foi desenhado para avaliar a for&#231;a de evid&#234;ncia dos benef&#237;cios de diferentes interven&#231;&#245;es nutricionais na remiss&#227;o da SM. A busca virtual foi realizada nas bases de dados Medline, Cochrane Library e PubMed, de ensaios cl&#237;nicos randomizados publicados no per&#237;odo entre 1999 a 2009, em qualquer l&#237;ngua, em indiv&#237;duos com 18 anos ou mais e diagn&#243;stico de SM, independente do crit&#233;rio. O operador booleano and foi utilizado na combina&#231;&#227;o dos MeSH terms "Metabolic Syndrome", "S&#237;ndrome x Metab&#243;lica" e "Metabolic Syndrome X"; dos entry terms "Dysmetabolic Syndrome X", Metabolic Cardiovascular Syndrome", "Metabolic X Syndrome", "Syndrome X, Metabolic" adicionados dos termos "diet", "intervention and diet", "treatment and diet" e "supplementation". Para cada estudo inclu&#237;do na revis&#227;o foi estimada a Preval&#234;ncia de SM e o C&#225;lculo da Efic&#225;cia ap&#243;s o per&#237;odo de seguimento. Medidas de risco relativo para cada estudo foram descritas pelo Forest Plot. Foram identificados 131 artigos, os quais ap&#243;s crit&#233;rios de elegibilidade resultaram em 15 estudos. Estes foram separados em quatro grupos: dieta normocal&#243;rica associada a exerc&#237;cios; dieta normocal&#243;rica isolada; dieta hipocal&#243;rica associada a exerc&#237;cios; e dieta hipocal&#243;rica isolada. Os ensaios com dieta hipocal&#243;rica associada &#224; pr&#225;tica de exerc&#237;cios apresentaram valores mais elevados de efic&#225;cia, colaborando para ressaltar os aspectos globais da mudan&#231;a do estilo de vida no tratamento da SM, onde a alimenta&#231;&#227;o saud&#225;vel e reduzida em calorias deve ser complementada com a pr&#225;tica de atividade f&#237;sica.</p>
      </abstract>
      <kwd-group xml:lang="pt" kwd-group-type="author-generated">
        <kwd>S&#237;ndrome metab&#243;lica</kwd>
        <kwd>ensaios cl&#237;nicos</kwd>
        <kwd>exerc&#237;cio</kwd>
        <kwd>dieta com restri&#231;&#227;o de gorduras</kwd>
        <kwd>medicina baseada em evid&#234;ncias</kwd>
      </kwd-group>
      <pub-date publication-format="electronic" date-type="pub">
        <day>21</day>
        <month>10</month>
        <year>2011</year>
      </pub-date>
    </article-meta>
  </front>
  <body>
    <p>
      <bold>ARTIGO DE REVIS&#195;O</bold>
    </p>
    <p>
      <bold>Interven&#231;&#245;es nutricionais em S&#237;ndrome Metab&#243;lica: uma revis&#227;o sistem&#225;tica</bold>
    </p>
    <p>
      <bold>Leila Sicupira Carneiro de Souza Le&#227;o; Milena Miranda de Moraes; Giulia Xavier de Carvalho; Rosalina Jorge Koifman</bold>
    </p>
    <p>Universidade Federal do Estado do Rio de Janeiro, FIOCRUZ/Escola Nacional de Sa&#250;de P&#250;blica, Rio de Janeiro, RJ - Brasil</p>
    <p>
      <xref ref-type="corresp" rid="back">Correspond&#234;ncia</xref>
    </p>
    <p>
      <bold>RESUMO</bold>
    </p>
    <p>N&#227;o existe consenso sobre a estrat&#233;gia nutricional mais adequada para tratar a S&#237;ndrome Metab&#243;lica (SM), de tal forma que ocorra redu&#231;&#227;o do risco cardiovascular. O presente estudo foi desenhado para avaliar a for&#231;a de evid&#234;ncia dos benef&#237;cios de diferentes interven&#231;&#245;es nutricionais na remiss&#227;o da SM. A busca virtual foi realizada nas bases de dados <italic>Medline, Cochrane Library</italic> e <italic>PubMed</italic>, de ensaios cl&#237;nicos randomizados publicados no per&#237;odo entre 1999 a 2009, em qualquer l&#237;ngua, em indiv&#237;duos com 18 anos ou mais e diagn&#243;stico de SM, independente do crit&#233;rio. O operador booleano <italic>and</italic> foi utilizado na combina&#231;&#227;o dos <italic>MeSH terms</italic> "<italic>Metabolic Syndrome</italic>", "S&#237;ndrome x Metab&#243;lica" e "<italic>Metabolic Syndrome X";</italic> dos <italic>entry terms</italic> "<italic>Dysmetabolic Syndrome X", Metabolic Cardiovascular Syndrome", "Metabolic X Syndrome", "Syndrome X, Metabolic"</italic> adicionados dos termos "<italic>diet</italic>", "<italic>intervention and diet</italic>", "<italic>treatment and diet</italic>" e "<italic>supplementation</italic>". Para cada estudo inclu&#237;do na revis&#227;o foi estimada a Preval&#234;ncia de SM e o C&#225;lculo da Efic&#225;cia ap&#243;s o per&#237;odo de seguimento. Medidas de risco relativo para cada estudo foram descritas pelo <italic>Forest Plot</italic>. Foram identificados 131 artigos, os quais ap&#243;s crit&#233;rios de elegibilidade resultaram em 15 estudos. Estes foram separados em quatro grupos: dieta normocal&#243;rica associada a exerc&#237;cios; dieta normocal&#243;rica isolada; dieta hipocal&#243;rica associada a exerc&#237;cios; e dieta hipocal&#243;rica isolada. Os ensaios com dieta hipocal&#243;rica associada &#224; pr&#225;tica de exerc&#237;cios apresentaram valores mais elevados de efic&#225;cia, colaborando para ressaltar os aspectos globais da mudan&#231;a do estilo de vida no tratamento da SM, onde a alimenta&#231;&#227;o saud&#225;vel e reduzida em calorias deve ser complementada com a pr&#225;tica de atividade f&#237;sica.</p>
    <p><bold>Palavras-chave: </bold> S&#237;ndrome metab&#243;lica, ensaios cl&#237;nicos, exerc&#237;cio, dieta com restri&#231;&#227;o de gorduras, medicina baseada em evid&#234;ncias.</p>
    <p>
      <bold>Introdu&#231;&#227;o</bold>
    </p>
    <p>A S&#237;ndrome Metab&#243;lica (SM) &#233; definida por um conjunto de ao menos tr&#234;s altera&#231;&#245;es, seja na press&#227;o arterial ou no metabolismo dos glic&#237;dios e lip&#237;dios, usualmente associada &#224;s doen&#231;as cardiovasculares, principal causa de morbimortalidade no Brasil<sup>1</sup>.</p>
    <p>N&#227;o existe consenso sobre a estrat&#233;gia nutricional mais adequada para tratar a SM. Embora as propostas atuais estejam relacionadas a mudan&#231;as comportamentais como modifica&#231;&#227;o dos h&#225;bitos alimentares e pr&#225;tica de atividade f&#237;sica<sup>2</sup>, as recomenda&#231;&#245;es nutricionais foram estabelecidas a partir de estudos realizados com pacientes saud&#225;veis ou que apresentavam as altera&#231;&#245;es metab&#243;licas isoladas<sup>3-8</sup>. Desta forma, sendo o tratamento eficaz para apenas um componente da s&#237;ndrome, ao inv&#233;s da remiss&#227;o do diagn&#243;stico, representada pela normaliza&#231;&#227;o de ao menos tr&#234;s caracter&#237;sticas, a prote&#231;&#227;o cardiovascular seria consequentemente menor.</p>
    <p>Neste contexto, o Projeto Diretrizes da Sociedade Brasileira de Endocrinologia<sup>4</sup>, ressalta a necessidade da realiza&#231;&#227;o de pesquisas que contribuam na defini&#231;&#227;o do tipo de interven&#231;&#227;o mais eficaz no tratamento de indiv&#237;duos com o diagn&#243;stico de SM.</p>
    <p>Devido &#224; aus&#234;ncia de revis&#245;es sistem&#225;ticas sobre o tema, o presente estudo foi desenhado para avaliar a for&#231;a de evid&#234;ncia dos benef&#237;cios de diferentes interven&#231;&#245;es nutricionais na remiss&#227;o da SM.</p>
    <p>
      <bold>M&#233;todos</bold>
    </p>
    <p>Foi realizada uma revis&#227;o sistem&#225;tica de estudos com interven&#231;&#245;es nutricionais, em indiv&#237;duos com SM diagnosticados pela presen&#231;a de ao menos tr&#234;s altera&#231;&#245;es conforme preconizado pela Organiza&#231;&#227;o Mundial de Sa&#250;de em 1999<sup>9</sup>. Al&#233;m desta publica&#231;&#227;o oficial, outros crit&#233;rios diagn&#243;sticos sugeridos pelos &#243;rg&#227;os NCEP-ATP III<sup>10</sup>, AHA<sup>11</sup>; IDF<sup>12</sup> e EGIR<sup>13</sup>, tamb&#233;m foram considerados, visto que representavam adapta&#231;&#245;es ou modifica&#231;&#245;es do crit&#233;rio oficial.</p>
    <p>A busca virtual foi realizada nas bases de dados <italic>Medline, Cochrane Library</italic> e <italic>PubMed</italic>, de ensaios cl&#237;nicos publicados no per&#237;odo entre 1999 a 2009, em qualquer l&#237;ngua. A avalia&#231;&#227;o dos crit&#233;rios de elegibilidade foi elaborada de forma independente por dois revisores e em caso de diverg&#234;ncias, um terceiro pesquisador era consultado.</p>
    <p>O operador booleano <italic>and</italic> foi utilizado na combina&#231;&#227;o dos <italic>MeSH terms</italic> "<italic>Metabolic Syndrome</italic>", "S&#237;ndrome x Metab&#243;lica" e "<italic>Metabolic Syndrome X";</italic> dos <italic>entry terms</italic> "<italic>Dysmetabolic Syndrome X", Metabolic Cardiovascular Syndrome", "Metabolic X Syndrome", "Syndrome X, Metabolic"</italic> adicionados dos termos "<italic>diet</italic>", "<italic>intervention and diet</italic>", "<italic>treatment and diet</italic>" e "<italic>supplementation</italic>". O tipo de publica&#231;&#227;o foi ensaio cl&#237;nico randomizado para todas as combina&#231;&#245;es de palavras.</p>
    <p>Os resumos dos artigos selecionados foram analisados para verificar se atendiam aos crit&#233;rios de inclus&#227;o que compreendiam: apresentar um delineamento de ensaio cl&#237;nico controlado com proposta de interven&#231;&#227;o nutricional; em popula&#231;&#227;o acima de 18 anos de idade; e considerar a remiss&#227;o da SM como desfecho. Foram exclu&#237;dos os estudos com interven&#231;&#245;es destinadas a tratar somente as altera&#231;&#245;es isoladas da SM.</p>
    <p>Na medida do poss&#237;vel, aderimos ao PRISMA<sup>14</sup> para relatar a presente revis&#227;o sistem&#225;tica. Ap&#243;s leitura dos artigos completos, os resultados foram sintetizados segundo o crit&#233;rio diagn&#243;stico da SM, a interven&#231;&#227;o nutricional, o grupo controle, o per&#237;odo da interven&#231;&#227;o e a preval&#234;ncia de SM, desfecho principal desta revis&#227;o.</p>
    <p>Para facilitar a compara&#231;&#227;o entre os estudos, foi calculada a efic&#225;cia das interven&#231;&#245;es por meio dos valores de preval&#234;ncia de SM ap&#243;s o per&#237;odo de seguimento, aplicados na f&#243;rmula proposta por Szklo e Javier Nieto<sup>15</sup>: (preval&#234;ncia no grupo controle - preval&#234;ncia grupo interven&#231;&#227;o/preval&#234;ncia grupo controle) x 100.</p>
    <p>Medidas de risco relativo para cada estudo foram descritas pelo <italic>Forest Plot</italic> elaborado no s<italic>oftware</italic> estat&#237;stico <italic>Review Manager</italic> vers&#227;o 5. Contudo, a meta-an&#225;lise estat&#237;stica n&#227;o foi justificada por causa da acentuada heterogeneidade dos estudos inclu&#237;dos.</p>
    <p>
      <bold>Resultados</bold>
    </p>
    <p>Na busca eletr&#244;nica, foram obtidas 131 publica&#231;&#245;es, das quais ap&#243;s leitura dos resumos e exclus&#227;o por incluir medicamentos, 59 artigos foram selecionados para an&#225;lise. Ap&#243;s exclus&#227;o de 44 artigos que n&#227;o atenderam aos crit&#233;rios de inclus&#227;o, 15 estudos foram inclu&#237;dos na revis&#227;o (<xref ref-type="fig" rid="f1">Figura 1</xref>).</p>
    <fig id="f1">
      <graphic xlink:href="1678-4170-abc-97-03-0260-00012-gf01.jpg"/></fig>
    <p>Todos os estudos selecionados eram ensaios cl&#237;nicos randomizados e foram publicados na l&#237;ngua inglesa. Quanto ao local de realiza&#231;&#227;o, It&#225;lia<sup>16-18</sup> contribuiu com tr&#234;s estudos, Estados Unidos da Am&#233;rica<sup>19-23</sup> com cinco, Finl&#226;ndia<sup>24,25</sup> com dois e Jap&#227;o<sup>26</sup>, Alemanha<sup>27</sup>, Ir&#227;<sup>28</sup>, Espanha<sup>29</sup> e Noruega<sup>30</sup> com um cada.</p>
    <p>As interven&#231;&#245;es apresentaram per&#237;odos entre 6 semanas e 31 meses, e envolveram 2089 participantes entre 24 e 75 anos, com &#205;ndice de Massa Corporal entre 26 e 43kg/m<sup>2</sup>. Dos quinze estudos, somente tr&#234;s citaram per&#237;odo de <italic>run in</italic><sup>16,25,28</sup>, e dois com interven&#231;&#227;o parcialmente cega<sup>17,20</sup>.</p>
    <p>Quanto &#224; popula&#231;&#227;o, quatro ensaios pesquisaram pacientes ambulatoriais provenientes de apenas 1 hospital<sup>18,22</sup>, dois foram multic&#234;ntricos<sup>24,29</sup>; dois com popula&#231;&#227;o representativa de comunidades<sup>16,30</sup>; tr&#234;s com pacientes captados por an&#250;ncios de jornais<sup>19,25,26</sup>; um com funcion&#225;rios de universidades<sup>20</sup> e tr&#234;s n&#227;o informaram a popula&#231;&#227;o estudada<sup>21,23,27</sup>.</p>
    <p>A preval&#234;ncia de SM foi o desfecho principal em seis estudos<sup>16,24-26,29,30</sup>, e secund&#225;ria onde a preval&#234;ncia dos componentes da SM<sup>18-22,27,28</sup>, a redu&#231;&#227;o ponderal<sup>23</sup> e o comportamento dos marcadores inflamat&#243;rios e de fun&#231;&#227;o endotelial<sup>17</sup> foram os desfechos principais.</p>
    <p>Os ensaios foram agrupados segundo o tipo de interven&#231;&#227;o, a saber: dieta normocal&#243;rica combinada a exerc&#237;cio f&#237;sico<sup>16,19</sup>; dieta normocal&#243;rica<sup>20,29</sup>; dieta hipocal&#243;rica combinada a exerc&#237;cio f&#237;sico<sup>24,25</sup>; e dieta hipocal&#243;rica<sup>22,27</sup> (<xref ref-type="table" rid="t01">Tabela 1</xref>).</p>
    <p content-type="asset">
      <table-wrap id="t01">
        <graphic xlink:href="1678-4170-abc-97-03-0260-00012-gt01.jpg"/></table-wrap>
    </p>
    <p>
      <bold>Dieta normocal&#243;rica combinada &#224; exerc&#237;cio f&#237;sico</bold>
    </p>
    <p>No estudo de Stewart e cols.<sup>19</sup>, o grupo interven&#231;&#227;o foi orientado a praticar exerc&#237;cios aer&#243;bicos supervisionados tr&#234;s vezes por semana, al&#233;m da dieta individualizada. Os controles receberam apenas orienta&#231;&#245;es gerais sobre alimenta&#231;&#227;o saud&#225;vel. De forma semelhante Bo e cols.<sup>16</sup> orientaram seus controles com informa&#231;&#245;es gerais, enquanto o grupo interven&#231;&#227;o recebeu orienta&#231;&#227;o nutricional individualizada e recomenda&#231;&#227;o de exerc&#237;cios.</p>
    <p>
      <bold>Dieta normocal&#243;rica</bold>
    </p>
    <p>No estudo de Mutungi e cols.<sup>20</sup>, a interven&#231;&#227;o foi caracterizada por dieta sem restri&#231;&#227;o energ&#233;tica, com baixo teor de carboidratos e acrescida de tr&#234;s ovos l&#237;quidos (Vistar<sup>&#174;</sup>) por dia. O grupo controle consumiu somente uma dieta de manuten&#231;&#227;o. Vale destacar que, embora a proposta diet&#233;tica fosse normocal&#243;rica, ambos os grupos reduziram o conte&#250;do energ&#233;tico da dieta at&#233; o final do seguimento.</p>
    <p>No ensaio de Salas-Salvad&#243; e cols.<sup>29</sup>, os dois grupos de interven&#231;&#227;o consumiram uma dieta mediterr&#226;nea suplementada com azeite de oliva extra-virgem (1,25L por semana), ou com oleaginosas (15g nozes/dia;7,5g avel&#227;s/dia; 7,5g am&#234;ndoas/dia). O grupo controle foi orientado somente com dieta normocal&#243;rica.</p>
    <p>
      <bold>Dieta hipocal&#243;rica combinada a exerc&#237;cio f&#237;sico</bold>
    </p>
    <p>O ensaio de Kukkonen-Harjula e cols.<sup>25</sup> submeteu os participantes a duas fases: uma redu&#231;&#227;o ponderal e outra de manuten&#231;&#227;o de peso com a interven&#231;&#227;o de interesse, a dieta acrescida de caminhada, e um grupo controle somente com a dieta. No estudo de Villareal e cols.<sup>21</sup>, a interven&#231;&#227;o consistia de dieta hipocal&#243;rica associada a exerc&#237;cios, enquanto ao grupo controle consumia apenas a dieta hipocal&#243;rica. Okura e cols.<sup>26</sup> ofertaram aos controles dieta hipocal&#243;rica com um suplemento alimentar (MicroDiet<sup>&#174;</sup>). O grupo interven&#231;&#227;o consumiu a mesma dieta associada &#224; pr&#225;tica de exerc&#237;cios.</p>
    <p>No estudo de Anderssen e cols.<sup>30</sup> o grupo do exerc&#237;cio combinado &#224; dieta foi supervisionado para realizar atividade aer&#243;bica tr&#234;s vezes por semana e consumo cal&#243;rico com restri&#231;&#227;o energ&#233;tica. Os controles consumiram apenas a dieta hipocal&#243;rica individualizada.</p>
    <p>No ensaio de Ilanne-Parikka e cols.<sup>24</sup> a interven&#231;&#227;o consistiu de orienta&#231;&#245;es para aumentar o n&#237;vel de atividade f&#237;sica, acr&#233;scimo de 15g de fibras para cada 1000kcal e ado&#231;&#227;o de dieta com baixo teor de gordura e colesterol. O grupo controle foi abordado apenas com orienta&#231;&#245;es gerais.</p>
    <p>
      <bold>Dieta hipocal&#243;rica</bold>
    </p>
    <p>O ensaio de Seshadri e cols.<sup>22</sup> ofertou dieta hipocal&#243;rica balanceada para o grupo controle enquanto o interven&#231;&#227;o foi orientado a consumir dieta hipocal&#243;rica pobre em carboidratos. Esposito e cols.<sup>17</sup> orientaram o grupo interven&#231;&#227;o com dieta mediterr&#226;nea, enquanto o controle orienta&#231;&#245;es gerais sobre alimenta&#231;&#227;o saud&#225;vel.</p>
    <p>No estudo de Azadbakht e cols.<sup>28</sup>, a interven&#231;&#227;o consistia na dieta <italic>DASH (Dietary Approaches to Stop Hypertension)</italic>, com d&#233;ficit de 500 kcal/dia, maior ingest&#227;o de frutas, vegetais, latic&#237;nios desnatados e menor teor de s&#243;dio.</p>
    <p>Muzio e cols.<sup>18</sup> realizaram interven&#231;&#227;o com 48% de carboidratos e o controle com 65%, ambos com d&#233;ficit de 500 kcal/dia e sess&#245;es mensais em grupo para orienta&#231;&#227;o nutricional e Katcher e cols.<sup>23</sup> compararam um grupo de dieta hipocal&#243;rica &#224; base de cereais integrais com outro que consumiu cereais refinados.</p>
    <p>O ensaio de K&#246;nig e cols.<sup>27</sup> orientou o grupo controle a consumir dieta hipocal&#243;rica e o grupo interven&#231;&#227;o a substituir duas refei&#231;&#245;es di&#225;rias por um iogurte de soja com mel (Almased<sup>&#174;</sup>).</p>
    <p>Considerando todos os estudos inclu&#237;dos na revis&#227;o, bem como os diferentes agrupamentos segundo tipo de interven&#231;&#227;o e correspondente c&#225;lculo da efic&#225;cia, observou-se que a dieta hipocal&#243;rica associada aos exerc&#237;cios f&#237;sicos apresentou melhor desempenho em rela&#231;&#227;o aos outros grupos, seguida pela normocal&#243;rica com exerc&#237;cios, hipocal&#243;rica isolada e normocal&#243;rica isolada.</p>
    <p>Contudo, independente do tipo de interven&#231;&#227;o nutricional, as medidas de efeito expressas no <italic>Forest Plot</italic> descrevem efeito protetor no risco de desenvolver SM para todas as propostas de tratamento nutricional analisadas (<xref ref-type="fig" rid="f02">Figura 2</xref>).</p>
    <p content-type="asset">
      <fig id="f02">
        <graphic xlink:href="1678-4170-abc-97-03-0260-00012-gf02.jpg"/></fig>
    </p>
    <p>
      <bold>Discuss&#227;o</bold>
    </p>
    <p>At&#233; quanto se conhece esta &#233; a &#250;nica revis&#227;o sistem&#225;tica que avaliou a for&#231;a de evid&#234;ncia de interven&#231;&#245;es nutricionais na remiss&#227;o do diagn&#243;stico de SM. Ap&#243;s uma extensa estrat&#233;gia de busca, a inclus&#227;o de apenas 15 estudos expressou a escassez da literatura quando se trata de avaliar o diagn&#243;stico da SM como desfecho categ&#243;rico principal ou secund&#225;rio.</p>
    <p>Al&#233;m da limita&#231;&#227;o quantitativa, a baixa qualidade e heterogeneidade dos estudos tamb&#233;m foi notada. Nenhum autor conduziu o ensaio segundo o guia CONSORT (<ext-link ext-link-type="uri" xlink:href="http://www.consort-statement.org/">http://www.consort-statement.org/</ext-link>), houve elevada variabilidade quanto ao tempo de interven&#231;&#227;o, alguns estudos desenharam grupos controle baseados apenas em orienta&#231;&#245;es gerais, enquanto outros dieta calculada, e a maioria, comparou grupos com amostras pequenas (&lt; 30 participantes).</p>
    <p>Estas caracter&#237;sticas, associadas ao pobre detalhamento da metodologia na maioria dos artigos impediram esclarecimento sobre o c&#225;lculo amostral, bem como informa&#231;&#245;es espec&#237;ficas do desenho da interven&#231;&#227;o proposta como cegamento e per&#237;odo de <italic>run in,</italic> impedindo uma meta-an&#225;lise dos resultados apresentados.</p>
    <p>Contudo, a efic&#225;cia das propostas hipocal&#243;ricas associadas &#224; atividade f&#237;sica foi semelhante &#224;s interven&#231;&#245;es realizadas em indiv&#237;duos com as altera&#231;&#245;es isoladas<sup>31-34</sup>, e refor&#231;am a sugest&#227;o de Reaven<sup>35</sup>, que prop&#244;s uma dieta reduzida em calorias associada &#224; atividade f&#237;sica para o tratamento de pacientes com SM.</p>
    <p>Pode-se considerar que a redu&#231;&#227;o cal&#243;rica da dieta &#233; a principal estrat&#233;gia para o tratamento do excesso de peso<sup>36</sup>, porque os aportes cal&#243;ricos reduzidos promovem a diminui&#231;&#227;o da massa adiposa atrav&#233;s de balan&#231;o energ&#233;tico negativo, condi&#231;&#227;o na qual o gasto energ&#233;tico supera o consumo de energia. Quando a redu&#231;&#227;o cal&#243;rica &#233; adicionada da pr&#225;tica de atividades f&#237;sicas, o efeito da redu&#231;&#227;o ponderal &#233; potencializado, especialmente em indiv&#237;duos com SM, onde a manuten&#231;&#227;o da massa magra aumentaria a sensibilidade &#224; insulina<sup>37</sup>.</p>
    <p>A import&#226;ncia da atividade f&#237;sica agregada a um planejamento alimentar ainda que normocal&#243;rico foi demonstrada nos estudos de Stewart e cols.<sup>19</sup> e Bo e cols.<sup>16</sup>. Mesmo com resultados de efic&#225;cia inferiores &#224;s interven&#231;&#245;es com dieta hipocal&#243;rica e exerc&#237;cios, as caracter&#237;sticas semelhantes de idade e IMC em ambos os grupos e a manuten&#231;&#227;o do consumo energ&#233;tico p&#243;s interven&#231;&#227;o refor&#231;am a influ&#234;ncia da atividade f&#237;sica na redu&#231;&#227;o ponderal. Ao mesmo tempo, a reduzida efic&#225;cia da dieta normocal&#243;rica n&#227;o associada &#224; atividade f&#237;sica de Salas-Salvad&#243; e cols.<sup>29</sup>, confirmou a necessidade de um balan&#231;o energ&#233;tico negativo no tratamento da SM, seja por redu&#231;&#227;o cal&#243;rica ou por aumento do gasto energ&#233;tico.</p>
    <p>Neste sentido, pode-se compreender as sugest&#245;es do Projeto Diretrizes<sup>4</sup> que valoriza a necessidade de redu&#231;&#227;o do conte&#250;do energ&#233;tico das propostas de tratamento para SM, em detrimento &#224;s mudan&#231;as na composi&#231;&#227;o em macronutrientes das mesmas. Para isso, recomendamos que ensaios cl&#237;nicos controlados randomizados e de alta qualidade sejam conduzidos para detectar os efeitos das exposi&#231;&#245;es diet&#233;ticas com seguran&#231;a e direcionar abordagens mais objetivas na medi&#231;&#227;o do consumo diet&#233;tico e desfechos de relev&#226;ncia na sa&#250;de p&#250;blica.</p>
    <p>A presente revis&#227;o sistem&#225;tica apresentou limita&#231;&#245;es como uma prov&#225;vel n&#227;o identifica&#231;&#227;o de todas as publica&#231;&#245;es, apesar da tentativa de minimizar esta possibilidade por meio da aplica&#231;&#227;o de termos amplos, da repeti&#231;&#227;o da busca nas bases de dados e nas refer&#234;ncias dos artigos selecionados. Como pontos fortes destacamos a abordagem sistem&#225;tica, a ampla busca em relevantes bases de dados, a inclus&#227;o de publica&#231;&#245;es em qualquer l&#237;ngua, e o rigor metodol&#243;gico.</p>
    <p>Embora o conjunto de interven&#231;&#245;es com dieta hipocal&#243;rica associada &#224; atividade f&#237;sica tenha apresentado resultados que se destacaram em rela&#231;&#227;o aos outros tipos de propostas nutricionais, a an&#225;lise conjunta dos estudos forneceu evid&#234;ncia dos benef&#237;cios do consumo de dietas individualizadas, pobres em gorduras saturadas, ricas em fibras, &#243;leos monoinsaturados, vitaminas e minerais na remiss&#227;o da S&#237;ndrome Metab&#243;lica.</p>
    <p>
      <bold>Conclus&#227;o</bold>
    </p>
    <p>Mesmo levando em considera&#231;&#227;o fatores que limitaram esta revis&#227;o sistem&#225;tica, pode-se concluir que a literatura cient&#237;fica sustenta os efeitos ben&#233;ficos da dieta hipocal&#243;rica associada &#224; pr&#225;tica de exerc&#237;cios f&#237;sicos, refor&#231;ando a import&#226;ncia da mudan&#231;a do estilo de vida no manejo da SM.</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 parcialmente financiado pela UNIRIO e FIOCRUZ.</p>
    <p>
      <bold>Vincula&#231;&#227;o Acad&#234;mica</bold>
    </p>
    <p>Este artigo &#233; parte de tese de Doutorado de Leila Sicupira Carneiro de Souza Le&#227;o pela Escola Nacional de Sa&#250;de P&#250;blica - FIOCRUZ.</p>
    <p>
      <fn id="back" fn-type="corresp">
        <p>Correspond&#234;ncia:</p>
        <p> Leila Sicupira Carneiro de Souza Le&#227;o </p>
        <p> Rua Nicanor Nunes, 102, quadra 17, lote 26 - Piratininga </p>
        <p> 24350-460 - Niter&#243;i, RJ - Brasil </p>
        <p> E-mail: </p>
        <p><email xlink:href="leilaleao@gmail.com">leilaleao@gmail.com</email>, </p>
        <p>
          <email xlink:href="rosalina.koifman@hotmail.com">rosalina.koifman@hotmail.com</email>
        </p>
      </fn>
    </p>
    <p>Artigo recebido em 05/04/10; revisado recebido em 29/06/10; aceito em 16/08/10. </p>
  </body>
  <back>
    <ref-list>
      <ref id="B1">
        <label>1</label>
        <mixed-citation>1. Minist&#233;rio da Sa&#250;de. Secretaria de Vigil&#226;ncia em Sa&#250;de. Uma an&#225;lise da situa&#231;&#227;o de sa&#250;de. Perfil de Mortalidade do Brasileiro. Bras&#237;lia, 6 de novembro de 2008. [Citado em 2008 nov 8]. Dispon&#237;vel em: <ext-link ext-link-type="uri" xlink:href="http://www.saude.gov.br">http://www.saude.gov.br</ext-link>.</mixed-citation>
        <element-citation publication-type="book">
          <source>Uma an&#225;lise da situa&#231;&#227;o de sa&#250;de: Perfil de Mortalidade do Brasileiro</source>
          <date>
            <month>11</month>
            <day>06</day>
            <year>2008</year>
          </date>
        </element-citation>
      </ref>
      <ref id="B2">
        <mixed-citation>2. Deen D. Metabolic    syndrome: time for action. Am Fam Physician. 2004; 69 (12): 2875-82.</mixed-citation>
        <element-citation publication-type="journal">
          <article-title>Metabolic syndrome: time for action</article-title>
          <source>Am Fam Physician</source>
          <date>
            <year>2004</year>
          </date>
          <fpage>2875</fpage>
          <lpage>82</lpage>
          <issue>12</issue>
          <volume>69</volume>
          <person-group person-group-type="author">
            <name>
              <surname>Deen</surname>
              <given-names>D</given-names>
            </name>
          </person-group>
        </element-citation>
      </ref>
      <ref id="B3">
        <mixed-citation>3. Carvalho MHC,    Brand&#227;o AP, Brand&#227;o AA, Nogueira AR, Suplicy H, Guimar&#227;es    JI, et al. / Sociedade Brasileira de Hipertens&#227;o / Sociedade Brasileira    de Cardiologia / Sociedade Brasileira de Endocrinologia e Metabologia / Sociedade    Brasileira de Diabetes. I Diretriz brasileira de diagn&#243;stico e tratamento    da s&#237;ndrome metab&#243;lica. Arq Bras Cardiol. 2005; 84 (supl 1): 3-28.</mixed-citation>
        <element-citation publication-type="journal">
          <article-title>I Diretriz brasileira de diagn&#243;stico e tratamento da s&#237;ndrome metab&#243;lica</article-title>
          <source>Arq Bras Cardiol</source>
          <date>
            <year>2005</year>
          </date>
          <fpage>3</fpage>
          <lpage>28</lpage>
          <volume>84</volume>
          <person-group person-group-type="author">
            <name>
              <surname>Carvalho</surname>
              <given-names>MHC</given-names>
            </name>
            <name>
              <surname>Brand&#227;o</surname>
              <given-names>AP</given-names>
            </name>
            <name>
              <surname>Brand&#227;o</surname>
              <given-names>AA</given-names>
            </name>
            <name>
              <surname>Nogueira</surname>
              <given-names>AR</given-names>
            </name>
            <name>
              <surname>Suplicy</surname>
              <given-names>H</given-names>
            </name>
            <name>
              <surname>Guimar&#227;es</surname>
              <given-names>JI</given-names>
            </name>
          </person-group>
        </element-citation>
      </ref>
      <ref id="B4">
        <label>4</label>
        <mixed-citation>4. Sociedade Brasileira de Endocrinologia e Metabologia. Projeto diretrizes: S&#237;ndrome Metab&#243;lica: tratamento n&#227;o-farmacol&#243;gico para redu&#231;&#227;o do risco cardiovascular. 2006. [citado em 2008 ago 19]. Dispon&#237;vel em: <ext-link ext-link-type="uri" xlink:href="http://www.projetodiretrizes.org.br/5_volume/38-SindrMeta.pdf">http://www.projetodiretrizes.org.br/5_volume/38-SindrMeta.pdf</ext-link>.</mixed-citation>
        <element-citation publication-type="book">
          <source>Projeto diretrizes: S&#237;ndrome Metab&#243;lica: tratamento n&#227;o-farmacol&#243;gico para redu&#231;&#227;o do risco cardiovascular</source>
          <date>
            <year>2006</year>
          </date>
        </element-citation>
      </ref>
      <ref id="B5">
        <mixed-citation>5. Hooper L, Bartlett    C, Davey SG, Ebrahim S. Advice to reduce dietary salt for prevention of cardiovascular    disease. Cochrane Databse Syst Rev. 2004; (1): CD003656.</mixed-citation>
        <element-citation publication-type="journal">
          <article-title>Advice to reduce dietary salt for prevention of cardiovascular disease</article-title>
          <source>Cochrane Databse Syst Rev</source>
          <date>
            <year>2004</year>
          </date>
          <fpage>CD003656</fpage>
          <issue>1</issue>
          <person-group person-group-type="author">
            <name>
              <surname>Hooper</surname>
              <given-names>L</given-names>
            </name>
            <name>
              <surname>Bartlett</surname>
              <given-names>C</given-names>
            </name>
            <name>
              <surname>Davey</surname>
              <given-names>SG</given-names>
            </name>
            <name>
              <surname>Ebrahim</surname>
              <given-names>S</given-names>
            </name>
          </person-group>
        </element-citation>
      </ref>
      <ref id="B6">
        <mixed-citation>6. Hooper L, Summerbell    CD, Higgins JP, Thompson RL, Clements G, Capps N, et al. Reduced or modified    dietary fat for preventing cardiovascular disease. Cochrane Database Syst Rev.    2001; (3): CD002137.</mixed-citation>
        <element-citation publication-type="journal">
          <article-title>Reduced or modified dietary fat for preventing cardiovascular disease</article-title>
          <source>Cochrane Database Syst Rev</source>
          <date>
            <year>2001</year>
          </date>
          <fpage>CD002137</fpage>
          <issue>3</issue>
          <person-group person-group-type="author">
            <name>
              <surname>Hooper</surname>
              <given-names>L</given-names>
            </name>
            <name>
              <surname>Summerbell</surname>
              <given-names>CD</given-names>
            </name>
            <name>
              <surname>Higgins</surname>
              <given-names>JP</given-names>
            </name>
            <name>
              <surname>Thompson</surname>
              <given-names>RL</given-names>
            </name>
            <name>
              <surname>Clements</surname>
              <given-names>G</given-names>
            </name>
            <name>
              <surname>Capps</surname>
              <given-names>N</given-names>
            </name>
          </person-group>
        </element-citation>
      </ref>
      <ref id="B7">
        <mixed-citation>7. Vollmer WM,    Sacks FM, Ard J, Appel LJ, Bray GA, Simon-Morton DG, et al. Effects of diet    and sodium intake on blood pressure: subgroup analysis of the DASH-sodium trial.    Ann Intern Med. 2001; 135 (12): 1019-28.</mixed-citation>
        <element-citation publication-type="journal">
          <article-title>Effects of diet and sodium intake on blood pressure: subgroup analysis of the DASH-sodium trial</article-title>
          <source>Ann Intern Med</source>
          <date>
            <year>2001</year>
          </date>
          <fpage>1019</fpage>
          <lpage>28</lpage>
          <issue>12</issue>
          <volume>135</volume>
          <person-group person-group-type="author">
            <name>
              <surname>Vollmer</surname>
              <given-names>WM</given-names>
            </name>
            <name>
              <surname>Sacks</surname>
              <given-names>FM</given-names>
            </name>
            <name>
              <surname>Ard</surname>
              <given-names>J</given-names>
            </name>
            <name>
              <surname>Appel</surname>
              <given-names>LJ</given-names>
            </name>
            <name>
              <surname>Bray</surname>
              <given-names>GA</given-names>
            </name>
            <name>
              <surname>Simon-Morton</surname>
              <given-names>DG</given-names>
            </name>
          </person-group>
        </element-citation>
      </ref>
      <ref id="B8">
        <mixed-citation>8. Trichopoulou    A, Costacou T, Bamia C, Trichopoulos D. Adherence to a Mediterranean diet and    survival in a Greek population. N Engl J Med. 2003; 348 (26): 2599-608.</mixed-citation>
        <element-citation publication-type="journal">
          <article-title>Adherence to a Mediterranean diet and survival in a Greek population</article-title>
          <source>N Engl J Med</source>
          <date>
            <year>2003</year>
          </date>
          <fpage>2599</fpage>
          <lpage>608</lpage>
          <issue>26</issue>
          <volume>348</volume>
          <person-group person-group-type="author">
            <name>
              <surname>Trichopoulou</surname>
              <given-names>A</given-names>
            </name>
            <name>
              <surname>Costacou</surname>
              <given-names>T</given-names>
            </name>
            <name>
              <surname>Bamia</surname>
              <given-names>C</given-names>
            </name>
            <name>
              <surname>Trichopoulos</surname>
              <given-names>D</given-names>
            </name>
          </person-group>
        </element-citation>
      </ref>
      <ref id="B9">
        <label>9</label>
        <mixed-citation>9. World Health Organization. Definition, diagnosis and classification of diabetes mellitus and its complications: report of a WHO consultation. Washington; 1999.</mixed-citation>
        <element-citation publication-type="book">
          <source>Definition, diagnosis and classification of diabetes mellitus and its complications: report of a WHO consultation</source>
          <date>
            <year>1999</year>
          </date>
        </element-citation>
      </ref>
      <ref id="B10">
        <mixed-citation>10. Executive Summary    of the Third Report of the National Cholesterol Education Program (NECP). Expert    Panel on Detection Evaluation, and Treatment of High Blood Cholesterol in Adults    (Adult Treatment Panel III). JAMA. 2001; 285 (19): 2486-97.</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)</article-title>
          <source>JAMA</source>
          <date>
            <year>2001</year>
          </date>
          <fpage>2486</fpage>
          <lpage>97</lpage>
          <issue>19</issue>
          <volume>285</volume>
          <person-group person-group-type="author">
            <name>
              <surname>Executive Summary of the Third Report of the National Cholesterol Education Program</surname>
              <given-names>(NECP)</given-names>
            </name>
          </person-group>
        </element-citation>
      </ref>
      <ref id="B11">
        <mixed-citation>11. Grundy SM,    Brewer HB, Cleeman JI, Smith SC, Lenfant C. Definition of metabolic syndrome:    report of the National Heart, Lung, and Blood Institute/American Heart Association    conference on scientific issues related to definition. Arterioscler Thromb Vasc    Biol. 2004; 24 (2): e13-8.</mixed-citation>
        <element-citation publication-type="journal">
          <article-title>Definition of metabolic syndrome: report of the National Heart, Lung, and Blood Institute/American Heart Association conference on scientific issues related to definition</article-title>
          <source>Arterioscler Thromb Vasc Biol</source>
          <date>
            <year>2004</year>
          </date>
          <fpage>e13</fpage>
          <lpage>8</lpage>
          <issue>2</issue>
          <volume>24</volume>
          <person-group person-group-type="author">
            <name>
              <surname>Grundy</surname>
              <given-names>SM</given-names>
            </name>
            <name>
              <surname>Brewer</surname>
              <given-names>HB</given-names>
            </name>
            <name>
              <surname>Cleeman</surname>
              <given-names>JI</given-names>
            </name>
            <name>
              <surname>Smith</surname>
              <given-names>SC</given-names>
            </name>
            <name>
              <surname>Lenfant</surname>
              <given-names>C</given-names>
            </name>
          </person-group>
        </element-citation>
      </ref>
      <ref id="B12">
        <label>12</label>
        <mixed-citation>12. International Diabetes Federation. [homepage na Internet]. The IDF consensus worldwide definition of the Metabolic Syndrome. [citado 2008 out 10]. Dispon&#237;vel em <ext-link ext-link-type="uri" xlink:href="http://www.idf.org">http://www.idf.org</ext-link>.</mixed-citation>
        <element-citation publication-type="book">
          <source>The IDF consensus worldwide definition of the Metabolic Syndrome</source>
        </element-citation>
      </ref>
      <ref id="B13">
        <mixed-citation>13. Balkau B, Charles    MA. Comment on the provisional report from the WHO Consultation. European Group    of the Study of Insulin Resistance (EGIR). Diabet Med.1999; 16 (5): 442-3.</mixed-citation>
        <element-citation publication-type="journal">
          <article-title>Comment on the provisional report from the WHO Consultation: European Group of the Study of Insulin Resistance (EGIR)</article-title>
          <source>Diabet Med</source>
          <date>
            <year>1999</year>
          </date>
          <fpage>442</fpage>
          <lpage>3</lpage>
          <issue>5</issue>
          <volume>16</volume>
          <person-group person-group-type="author">
            <name>
              <surname>Balkau</surname>
              <given-names>B</given-names>
            </name>
            <name>
              <surname>Charles</surname>
              <given-names>MA</given-names>
            </name>
          </person-group>
        </element-citation>
      </ref>
      <ref id="B14">
        <mixed-citation>14. Moher D, Liberati    A, Tetzlaff J, Altman DG. Preferred reporting items for systematic reviews and    meta-analyses: the PRISMA statement. J Clin Epidemiol. 2009; 62 (10): 1006-12.</mixed-citation>
        <element-citation publication-type="journal">
          <article-title>Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement</article-title>
          <source>J Clin Epidemiol</source>
          <date>
            <year>2009</year>
          </date>
          <fpage>1006</fpage>
          <lpage>12</lpage>
          <issue>10</issue>
          <volume>62</volume>
          <person-group person-group-type="author">
            <name>
              <surname>Moher</surname>
              <given-names>D</given-names>
            </name>
            <name>
              <surname>Liberati</surname>
              <given-names>A</given-names>
            </name>
            <name>
              <surname>Tetzlaff</surname>
              <given-names>J</given-names>
            </name>
            <name>
              <surname>Altman</surname>
              <given-names>DG</given-names>
            </name>
          </person-group>
        </element-citation>
      </ref>
      <ref id="B15">
        <mixed-citation>15. Szklo M, Javier    Nieto, F. Epidemiology beyond the basics. Maryland: Aspen Publication; 2000.</mixed-citation>
        <element-citation publication-type="book">
          <source>Epidemiology beyond the basics</source>
          <date>
            <year>2000</year>
          </date>
          <person-group person-group-type="author">
            <name>
              <surname>Szklo</surname>
              <given-names>M</given-names>
            </name>
            <name>
              <surname>Javier Nieto</surname>
              <given-names>F</given-names>
            </name>
          </person-group>
        </element-citation>
      </ref>
      <ref id="B16">
        <mixed-citation>16. Bo S, Ciccone    G, Baldi C, Benini L, Dusio F, Forastiere G, et al. Effectiveness of a lifestyle    intervention on metabolic syndrome: a randomized controlled trial. J Gen Intern    Med. 2007; 22 (12): 1695-703.</mixed-citation>
        <element-citation publication-type="journal">
          <article-title>Effectiveness of a lifestyle intervention on metabolic syndrome: a randomized controlled trial</article-title>
          <source>J Gen Intern Med</source>
          <date>
            <year>2007</year>
          </date>
          <fpage>1695</fpage>
          <lpage>703</lpage>
          <issue>12</issue>
          <volume>22</volume>
          <person-group person-group-type="author">
            <name>
              <surname>Bo</surname>
              <given-names>S</given-names>
            </name>
            <name>
              <surname>Ciccone</surname>
              <given-names>G</given-names>
            </name>
            <name>
              <surname>Baldi</surname>
              <given-names>C</given-names>
            </name>
            <name>
              <surname>Benini</surname>
              <given-names>L</given-names>
            </name>
            <name>
              <surname>Dusio</surname>
              <given-names>F</given-names>
            </name>
            <name>
              <surname>Forastiere</surname>
              <given-names>G</given-names>
            </name>
          </person-group>
        </element-citation>
      </ref>
      <ref id="B17">
        <mixed-citation>17. Esposito K,    Marfella R, Ciotola M, Di Palo C, Giugliano F, Giugliano G, et al. Effect of    a Mediterranean-Style diet on endothelial dysfunction and markers of vascular    inflammation in the metabolic syndrome. JAMA. 2004; 292 (12): 1440-6.</mixed-citation>
        <element-citation publication-type="journal">
          <article-title>Effect of a Mediterranean-Style diet on endothelial dysfunction and markers of vascular inflammation in the metabolic syndrome</article-title>
          <source>JAMA</source>
          <date>
            <year>2004</year>
          </date>
          <fpage>1440</fpage>
          <lpage>6</lpage>
          <issue>12</issue>
          <volume>292</volume>
          <person-group person-group-type="author">
            <name>
              <surname>Esposito</surname>
              <given-names>K</given-names>
            </name>
            <name>
              <surname>Marfella</surname>
              <given-names>R</given-names>
            </name>
            <name>
              <surname>Ciotola</surname>
              <given-names>M</given-names>
            </name>
            <name>
              <surname>Di Palo</surname>
              <given-names>C</given-names>
            </name>
            <name>
              <surname>Giugliano</surname>
              <given-names>F</given-names>
            </name>
            <name>
              <surname>Giugliano</surname>
              <given-names>G</given-names>
            </name>
          </person-group>
        </element-citation>
      </ref>
      <ref id="B18">
        <mixed-citation>18. Muzio F, Mondazzi    L, Harris WS, Sommariva D, Branchi A. Effects of moderate variations in the    macronutrient content of the diet on cardiovascular disease risk factors in    obese patients with the metabolic syndrome. Am J Clin Nutr. 2007; 86 (4): 946-51.</mixed-citation>
        <element-citation publication-type="journal">
          <article-title>Effects of moderate variations in the macronutrient content of the diet on cardiovascular disease risk factors in obese patients with the metabolic syndrome</article-title>
          <source>Am J Clin Nutr</source>
          <date>
            <year>2007</year>
          </date>
          <fpage>946</fpage>
          <lpage>51</lpage>
          <issue>4</issue>
          <volume>86</volume>
          <person-group person-group-type="author">
            <name>
              <surname>Muzio</surname>
              <given-names>F</given-names>
            </name>
            <name>
              <surname>Mondazzi</surname>
              <given-names>L</given-names>
            </name>
            <name>
              <surname>Harris</surname>
              <given-names>WS</given-names>
            </name>
            <name>
              <surname>Sommariva</surname>
              <given-names>D</given-names>
            </name>
            <name>
              <surname>Branchi</surname>
              <given-names>A</given-names>
            </name>
          </person-group>
        </element-citation>
      </ref>
      <ref id="B19">
        <mixed-citation>19. Stewart KJ,    Bacher AC, Turner K, Lim JG, Hees PS, Shapiro EP, et al. Exercise and risk factors    associated with metabolic syndrome in older adults. Am J Prev Med. 2005; 28    (1): 9-18.</mixed-citation>
        <element-citation publication-type="journal">
          <article-title>Exercise and risk factors associated with metabolic syndrome in older adults</article-title>
          <source>Am J Prev Med</source>
          <date>
            <year>2005</year>
          </date>
          <fpage>9</fpage>
          <lpage>18</lpage>
          <issue>1</issue>
          <volume>28</volume>
          <person-group person-group-type="author">
            <name>
              <surname>Stewart</surname>
              <given-names>KJ</given-names>
            </name>
            <name>
              <surname>Bacher</surname>
              <given-names>AC</given-names>
            </name>
            <name>
              <surname>Turner</surname>
              <given-names>K</given-names>
            </name>
            <name>
              <surname>Lim</surname>
              <given-names>JG</given-names>
            </name>
            <name>
              <surname>Hees</surname>
              <given-names>PS</given-names>
            </name>
            <name>
              <surname>Shapiro</surname>
              <given-names>EP</given-names>
            </name>
          </person-group>
        </element-citation>
      </ref>
      <ref id="B20">
        <mixed-citation>20. Mutungi G,    Ratliff, Puglisi M, Torres-Gonzalez M, Vaishnav U, Leite JO, et al. Dietary    cholesterol from eggs increases plasma HDL cholesterol in overweight men consuming    a carbohydrate-restricted diet. J Nutr. 2008; 138 (2): 272-6.</mixed-citation>
        <element-citation publication-type="journal">
          <article-title>Dietary cholesterol from eggs increases plasma HDL cholesterol in overweight men consuming a carbohydrate-restricted diet</article-title>
          <source>J Nutr</source>
          <date>
            <year>2008</year>
          </date>
          <fpage>272</fpage>
          <lpage>6</lpage>
          <issue>2</issue>
          <volume>138</volume>
          <person-group person-group-type="author">
            <name>
              <surname>Mutungi</surname>
              <given-names>G</given-names>
            </name>
            <name>
              <surname>Ratliff</surname>
            </name>
            <name>
              <surname>Puglisi</surname>
              <given-names>M</given-names>
            </name>
            <name>
              <surname>Torres-Gonzalez</surname>
              <given-names>M</given-names>
            </name>
            <name>
              <surname>Vaishnav</surname>
              <given-names>U</given-names>
            </name>
            <name>
              <surname>Leite</surname>
              <given-names>JO</given-names>
            </name>
          </person-group>
        </element-citation>
      </ref>
      <ref id="B21">
        <mixed-citation>21. Villareal DT,    Miller BV, Banks M, Fontana L, Sinacore DR, Klein S. Effect of lifestyle intervention    on metabolic coronary heart disease risk factors in obese older adults. Am J    Clin Nutr. 2006; 84 (6): 1317-23.</mixed-citation>
        <element-citation publication-type="journal">
          <article-title>Effect of lifestyle intervention on metabolic coronary heart disease risk factors in obese older adults</article-title>
          <source>Am J Clin Nutr</source>
          <date>
            <year>2006</year>
          </date>
          <fpage>1317</fpage>
          <lpage>23</lpage>
          <issue>6</issue>
          <volume>84</volume>
          <person-group person-group-type="author">
            <name>
              <surname>Villareal</surname>
              <given-names>DT</given-names>
            </name>
            <name>
              <surname>Miller</surname>
              <given-names>BV</given-names>
            </name>
            <name>
              <surname>Banks</surname>
              <given-names>M</given-names>
            </name>
            <name>
              <surname>Fontana</surname>
              <given-names>L</given-names>
            </name>
            <name>
              <surname>Sinacore</surname>
              <given-names>DR</given-names>
            </name>
            <name>
              <surname>Klein</surname>
              <given-names>S</given-names>
            </name>
          </person-group>
        </element-citation>
      </ref>
      <ref id="B22">
        <mixed-citation>22. Seshadri P,    Iqbal N, Stern L, Williams M, Chicano KL, Daily DA, et al. A randomized study    comparing the effects of a low-carbohydrate diet and a conventional diet on    lipoprotein subfractions and C-reactive protein levels in patients with severe    obesity. Am J Med. 2004; 117 (6): 398-405.</mixed-citation>
        <element-citation publication-type="journal">
          <article-title>A randomized study comparing the effects of a low-carbohydrate diet and a conventional diet on lipoprotein subfractions and C-reactive protein levels in patients with severe obesity</article-title>
          <source>Am J Med</source>
          <date>
            <year>2004</year>
          </date>
          <fpage>398</fpage>
          <lpage>405</lpage>
          <issue>6</issue>
          <volume>117</volume>
          <person-group person-group-type="author">
            <name>
              <surname>Seshadri</surname>
              <given-names>P</given-names>
            </name>
            <name>
              <surname>Iqbal</surname>
              <given-names>N</given-names>
            </name>
            <name>
              <surname>Stern</surname>
              <given-names>L</given-names>
            </name>
            <name>
              <surname>Williams</surname>
              <given-names>M</given-names>
            </name>
            <name>
              <surname>Chicano</surname>
              <given-names>KL</given-names>
            </name>
            <name>
              <surname>Daily</surname>
              <given-names>DA</given-names>
            </name>
          </person-group>
        </element-citation>
      </ref>
      <ref id="B23">
        <mixed-citation>23. Katcher HI,    Legro RS, Kunselman AR, Gillies PJ, Demers LM, Bagshaw DM, et al. The effects    of a whole grain-enriched hypocaloric diet on cardiovascular disease risk factors    in men and women with metabolic syndrome. Am J Clin Nutr. 2008; 87 (1): 79-90.</mixed-citation>
        <element-citation publication-type="journal">
          <article-title>The effects of a whole grain-enriched hypocaloric diet on cardiovascular disease risk factors in men and women with metabolic syndrome</article-title>
          <source>Am J Clin Nutr</source>
          <date>
            <year>2008</year>
          </date>
          <fpage>79</fpage>
          <lpage>90</lpage>
          <issue>1</issue>
          <volume>87</volume>
          <person-group person-group-type="author">
            <name>
              <surname>Katcher</surname>
              <given-names>HI</given-names>
            </name>
            <name>
              <surname>Legro</surname>
              <given-names>RS</given-names>
            </name>
            <name>
              <surname>Kunselman</surname>
              <given-names>AR</given-names>
            </name>
            <name>
              <surname>Gillies</surname>
              <given-names>PJ</given-names>
            </name>
            <name>
              <surname>Demers</surname>
              <given-names>LM</given-names>
            </name>
            <name>
              <surname>Bagshaw</surname>
              <given-names>DM</given-names>
            </name>
          </person-group>
        </element-citation>
      </ref>
      <ref id="B24">
        <mixed-citation>24. Ilanne-Parikka    P, Eriksson JG, Lindstr&#246;m J, Peltonen M, Aunola S, H&#228;m&#228;l&#228;inen    H, et al. Effect of lifestyle intervention on the occurrence of metabolic syndrome    and its components in the Finnish Diabetes Prevention Study. Diabetes Care.    2008; 31 (4): 805-7.</mixed-citation>
        <element-citation publication-type="journal">
          <article-title>Effect of lifestyle intervention on the occurrence of metabolic syndrome and its components in the Finnish Diabetes Prevention Study</article-title>
          <source>Diabetes Care</source>
          <date>
            <year>2008</year>
          </date>
          <fpage>805</fpage>
          <lpage>7</lpage>
          <issue>4</issue>
          <volume>31</volume>
          <person-group person-group-type="author">
            <name>
              <surname>Ilanne-Parikka</surname>
              <given-names>P</given-names>
            </name>
            <name>
              <surname>Eriksson</surname>
              <given-names>JG</given-names>
            </name>
            <name>
              <surname>Lindstr&#246;m</surname>
              <given-names>J</given-names>
            </name>
            <name>
              <surname>Peltonen</surname>
              <given-names>M</given-names>
            </name>
            <name>
              <surname>Aunola</surname>
              <given-names>S</given-names>
            </name>
            <name>
              <surname>H&#228;m&#228;l&#228;inen</surname>
              <given-names>H</given-names>
            </name>
          </person-group>
        </element-citation>
      </ref>
      <ref id="B25">
        <mixed-citation>25. Kukkonen-Harjula    KT, Borg PT, Nenonen AM, Fogelholm MG. Effects of a weight maintenance program    with or without exercise on the metabolic syndrome: a randomized trial in obese    men. Prev Med. 2005; 41 (3-4): 784-90.</mixed-citation>
        <element-citation publication-type="journal">
          <article-title>Effects of a weight maintenance program with or without exercise on the metabolic syndrome: a randomized trial in obese men</article-title>
          <source>Prev Med</source>
          <date>
            <year>2005</year>
          </date>
          <fpage>784</fpage>
          <lpage>90</lpage>
          <issue>3-4</issue>
          <volume>41</volume>
          <person-group person-group-type="author">
            <name>
              <surname>Kukkonen-Harjula</surname>
              <given-names>KT</given-names>
            </name>
            <name>
              <surname>Borg</surname>
              <given-names>PT</given-names>
            </name>
            <name>
              <surname>Nenonen</surname>
              <given-names>AM</given-names>
            </name>
            <name>
              <surname>Fogelholm</surname>
              <given-names>MG</given-names>
            </name>
          </person-group>
        </element-citation>
      </ref>
      <ref id="B26">
        <mixed-citation>26. Okura T, Nakata    Y, Ohkawara K, Numao S, Katayama Y, Matsuo T, et al. Effects of aerobic exercise    on metabolic syndrome improvement in response to weight reduction. Obesity.    2007; 15 (10): 2478-84.</mixed-citation>
        <element-citation publication-type="journal">
          <article-title>Effects of aerobic exercise on metabolic syndrome improvement in response to weight reduction</article-title>
          <source>Obesity</source>
          <date>
            <year>2007</year>
          </date>
          <fpage>2478</fpage>
          <lpage>84</lpage>
          <issue>10</issue>
          <volume>15</volume>
          <person-group person-group-type="author">
            <name>
              <surname>Okura</surname>
              <given-names>T</given-names>
            </name>
            <name>
              <surname>Nakata</surname>
              <given-names>Y</given-names>
            </name>
            <name>
              <surname>Ohkawara</surname>
              <given-names>K</given-names>
            </name>
            <name>
              <surname>Numao</surname>
              <given-names>S</given-names>
            </name>
            <name>
              <surname>Katayama</surname>
              <given-names>Y</given-names>
            </name>
            <name>
              <surname>Matsuo</surname>
              <given-names>T</given-names>
            </name>
          </person-group>
        </element-citation>
      </ref>
      <ref id="B27">
        <mixed-citation>27. K&#246;nig    D, Deibert P, Frey I, Landmann U, Berg A. Effect of meal replacement on metabolic    risk factors in overweight and obese subjects. Ann Nutr Metab. 2008; 52 (1):    74-8.</mixed-citation>
        <element-citation publication-type="journal">
          <article-title>Effect of meal replacement on metabolic risk factors in overweight and obese subjects</article-title>
          <source>Ann Nutr Metab</source>
          <date>
            <year>2008</year>
          </date>
          <fpage>74</fpage>
          <lpage>8</lpage>
          <issue>1</issue>
          <volume>52</volume>
          <person-group person-group-type="author">
            <name>
              <surname>K&#246;nig</surname>
              <given-names>D</given-names>
            </name>
            <name>
              <surname>Deibert</surname>
              <given-names>P</given-names>
            </name>
            <name>
              <surname>Frey</surname>
              <given-names>I</given-names>
            </name>
            <name>
              <surname>Landmann</surname>
              <given-names>U</given-names>
            </name>
            <name>
              <surname>Berg</surname>
              <given-names>A</given-names>
            </name>
          </person-group>
        </element-citation>
      </ref>
      <ref id="B28">
        <mixed-citation>28. Azadbakht L,    Mirmiran P, Esmaillzadeh A, Azizi T, Azizi F. Beneficial effects of a dietary    approaches to stop hypertension eating plan on features of the metabolic syndrome.    Diabetes Care. 2008; 28 (12): 2823-31.</mixed-citation>
        <element-citation publication-type="journal">
          <article-title>Beneficial effects of a dietary approaches to stop hypertension eating plan on features of the metabolic syndrome</article-title>
          <source>Diabetes Care</source>
          <date>
            <year>2008</year>
          </date>
          <fpage>2823</fpage>
          <lpage>31</lpage>
          <issue>12</issue>
          <volume>28</volume>
          <person-group person-group-type="author">
            <name>
              <surname>Azadbakht</surname>
              <given-names>L</given-names>
            </name>
            <name>
              <surname>Mirmiran</surname>
              <given-names>P</given-names>
            </name>
            <name>
              <surname>Esmaillzadeh</surname>
              <given-names>A</given-names>
            </name>
            <name>
              <surname>Azizi</surname>
              <given-names>T</given-names>
            </name>
            <name>
              <surname>Azizi</surname>
              <given-names>F</given-names>
            </name>
          </person-group>
        </element-citation>
      </ref>
      <ref id="B29">
        <mixed-citation>29. Salas-Salvad&#243;    J, Fernandez-Ballart J, Ros E, Martinez-Gonzalez MA, Fit&#243; M, Estruch    R, et al. Effect of a Mediterranean diet supplemented with nuts on metabolic    syndrome status: one-year results of the PREDIMED Randomized Trial. Arch Intern    Med. 2008; 168 (22): 2449-58.</mixed-citation>
        <element-citation publication-type="journal">
          <article-title>Effect of a Mediterranean diet supplemented with nuts on metabolic syndrome status: one-year results of the PREDIMED Randomized Trial</article-title>
          <source>Arch Intern Med</source>
          <date>
            <year>2008</year>
          </date>
          <fpage>2449</fpage>
          <lpage>58</lpage>
          <issue>22</issue>
          <volume>168</volume>
          <person-group person-group-type="author">
            <name>
              <surname>Salas-Salvad&#243;</surname>
              <given-names>J</given-names>
            </name>
            <name>
              <surname>Fernandez-Ballart</surname>
              <given-names>J</given-names>
            </name>
            <name>
              <surname>Ros</surname>
              <given-names>E</given-names>
            </name>
            <name>
              <surname>Martinez-Gonzalez</surname>
              <given-names>MA</given-names>
            </name>
            <name>
              <surname>Fit&#243;</surname>
              <given-names>M</given-names>
            </name>
            <name>
              <surname>Estruch</surname>
              <given-names>R</given-names>
            </name>
          </person-group>
        </element-citation>
      </ref>
      <ref id="B30">
        <mixed-citation>30. Anderssen SA,    Carroll S, Urdal P, Holme I. Combined diet and exercise intervention reverses    the metabolic syndrome in middle-aged males: results from the Oslo Diet and    Exercise Study. Scand J Med Sci Sports. 2007; 17 (6): 687-95.</mixed-citation>
        <element-citation publication-type="journal">
          <article-title>Combined diet and exercise intervention reverses the metabolic syndrome in middle-aged males: results from the Oslo Diet and Exercise Study</article-title>
          <source>Scand J Med Sci Sports</source>
          <date>
            <year>2007</year>
          </date>
          <fpage>687</fpage>
          <lpage>95</lpage>
          <issue>6</issue>
          <volume>17</volume>
          <person-group person-group-type="author">
            <name>
              <surname>Anderssen</surname>
              <given-names>SA</given-names>
            </name>
            <name>
              <surname>Carroll</surname>
              <given-names>S</given-names>
            </name>
            <name>
              <surname>Urdal</surname>
              <given-names>P</given-names>
            </name>
            <name>
              <surname>Holme</surname>
              <given-names>I</given-names>
            </name>
          </person-group>
        </element-citation>
      </ref>
      <ref id="B31">
        <mixed-citation>31. Jacobs DR,    Sluik D, Rockling-Andersen MH, Anderssen SA, Drevon CA. Association of 1-y changes    in diet pattern with cardiovascular disease risk factors and adipokines: results    from the 1-y randomized Oslo Diet and Exercise Study. Am J Clin Nutr. 2009;    89 (2): 509-17.</mixed-citation>
        <element-citation publication-type="journal">
          <article-title>Association of 1-y changes in diet pattern with cardiovascular disease risk factors and adipokines: results from the 1-y randomized Oslo Diet and Exercise Study</article-title>
          <source>Am J Clin Nutr</source>
          <date>
            <year>2009</year>
          </date>
          <fpage>509</fpage>
          <lpage>17</lpage>
          <issue>2</issue>
          <volume>89</volume>
          <person-group person-group-type="author">
            <name>
              <surname>Jacobs</surname>
              <given-names>DR</given-names>
            </name>
            <name>
              <surname>Sluik</surname>
              <given-names>D</given-names>
            </name>
            <name>
              <surname>Rockling-Andersen</surname>
              <given-names>MH</given-names>
            </name>
            <name>
              <surname>Anderssen</surname>
              <given-names>SA</given-names>
            </name>
            <name>
              <surname>Drevon</surname>
              <given-names>CA</given-names>
            </name>
          </person-group>
        </element-citation>
      </ref>
      <ref id="B32">
        <mixed-citation>32. Kuller LH,    Kinzel LS, Pettee KK, Kriska AM, Simkin-Silverman LR, Conroy MB, et al. Lifestyle    intervention and coronary heart disease risk factor changes over 18 months in    postmenopausal women: the women on the move through activity and nutrition (Woman    Study) clinical trial. J Womens Health. 2006; 15 (8): 962-74.</mixed-citation>
        <element-citation publication-type="journal">
          <article-title>Lifestyle intervention and coronary heart disease risk factor changes over 18 months in postmenopausal women: the women on the move through activity and nutrition (Woman Study) clinical trial</article-title>
          <source>J Womens Health</source>
          <date>
            <year>2006</year>
          </date>
          <fpage>962</fpage>
          <lpage>74</lpage>
          <issue>8</issue>
          <volume>15</volume>
          <person-group person-group-type="author">
            <name>
              <surname>Kuller</surname>
              <given-names>LH</given-names>
            </name>
            <name>
              <surname>Kinzel</surname>
              <given-names>LS</given-names>
            </name>
            <name>
              <surname>Pettee</surname>
              <given-names>KK</given-names>
            </name>
            <name>
              <surname>Kriska</surname>
              <given-names>AM</given-names>
            </name>
            <name>
              <surname>Simkin-Silverman</surname>
              <given-names>LR</given-names>
            </name>
            <name>
              <surname>Conroy</surname>
              <given-names>MB</given-names>
            </name>
          </person-group>
        </element-citation>
      </ref>
      <ref id="B33">
        <mixed-citation>33. Meckling KA,    Sherfey R. A randomized trial of a hypocaloric high-protein diet, with and without    exercise, on weight loss, fitness, and markers of the metabolic syndrome in    overweight and obese women. Appl Physiol Nutr Metab. 2007; 32 (4): 743-52.</mixed-citation>
        <element-citation publication-type="journal">
          <article-title>A randomized trial of a hypocaloric high-protein diet, with and without exercise, on weight loss, fitness, and markers of the metabolic syndrome in overweight and obese women</article-title>
          <source>Appl Physiol Nutr Metab</source>
          <date>
            <year>2007</year>
          </date>
          <fpage>743</fpage>
          <lpage>52</lpage>
          <issue>4</issue>
          <volume>32</volume>
          <person-group person-group-type="author">
            <name>
              <surname>Meckling</surname>
              <given-names>KA</given-names>
            </name>
            <name>
              <surname>Sherfey</surname>
              <given-names>R</given-names>
            </name>
          </person-group>
        </element-citation>
      </ref>
      <ref id="B34">
        <mixed-citation>34. Oh EG, Hyun    SS, Kim SH, Bang SY, Chu SH, Jeon JT, et al. A randomized controlled trial of    therapeutic lifestyle modification in rural women with metabolic syndrome: a    pilot study. Metabolism. 2008; 57 (2): 255-61.</mixed-citation>
        <element-citation publication-type="journal">
          <article-title>A randomized controlled trial of therapeutic lifestyle modification in rural women with metabolic syndrome: a pilot study</article-title>
          <source>Metabolism</source>
          <date>
            <year>2008</year>
          </date>
          <fpage>255</fpage>
          <lpage>61</lpage>
          <issue>2</issue>
          <volume>57</volume>
          <person-group person-group-type="author">
            <name>
              <surname>Oh</surname>
              <given-names>EG</given-names>
            </name>
            <name>
              <surname>Hyun</surname>
              <given-names>SS</given-names>
            </name>
            <name>
              <surname>Kim</surname>
              <given-names>SH</given-names>
            </name>
            <name>
              <surname>Bang</surname>
              <given-names>SY</given-names>
            </name>
            <name>
              <surname>Chu</surname>
              <given-names>SH</given-names>
            </name>
            <name>
              <surname>Jeon</surname>
              <given-names>JT</given-names>
            </name>
          </person-group>
        </element-citation>
      </ref>
      <ref id="B35">
        <mixed-citation>35. Reaven G. Banting    lecture 1988: role of insulin resistance in human disease. Diabetes. 1988; 37    (12): 1595-607.</mixed-citation>
        <element-citation publication-type="journal">
          <article-title>Banting lecture 1988: role of insulin resistance in human disease</article-title>
          <source>Diabetes</source>
          <date>
            <year>1988</year>
          </date>
          <fpage>1595</fpage>
          <lpage>607</lpage>
          <issue>12</issue>
          <volume>37</volume>
          <person-group person-group-type="author">
            <name>
              <surname>Reaven</surname>
              <given-names>G</given-names>
            </name>
          </person-group>
        </element-citation>
      </ref>
      <ref id="B36">
        <mixed-citation>36. Francischi    RPP, Pereira LO, Freitas CS. Obesidade: atualiza&#231;&#227;o sobre etiologia,    morbidade e tratamento. Rev Nutr. 2000; 13: 17-28.</mixed-citation>
        <element-citation publication-type="journal">
          <article-title>Obesidade: atualiza&#231;&#227;o sobre etiologia, morbidade e tratamento</article-title>
          <source>Rev Nutr</source>
          <date>
            <year>2000</year>
          </date>
          <fpage>17</fpage>
          <lpage>28</lpage>
          <volume>13</volume>
          <person-group person-group-type="author">
            <name>
              <surname>Francischi</surname>
              <given-names>RPP</given-names>
            </name>
            <name>
              <surname>Pereira</surname>
              <given-names>LO</given-names>
            </name>
            <name>
              <surname>Freitas</surname>
              <given-names>CS</given-names>
            </name>
          </person-group>
        </element-citation>
      </ref>
      <ref id="B37">
        <mixed-citation>37. Lyra R, Oliveira    M, Lins D, Cavalcanti N. Preven&#231;&#227;o do diabetes mellitus tipo 2.    Arq Bras Endocrinol Metab. 2006; 50 (2): 239-49.</mixed-citation>
        <element-citation publication-type="journal">
          <article-title>Preven&#231;&#227;o do diabetes mellitus tipo 2</article-title>
          <source>Arq Bras Endocrinol Metab</source>
          <date>
            <year>2006</year>
          </date>
          <fpage>239</fpage>
          <lpage>49</lpage>
          <issue>2</issue>
          <volume>50</volume>
          <person-group person-group-type="author">
            <name>
              <surname>Lyra</surname>
              <given-names>R</given-names>
            </name>
            <name>
              <surname>Oliveira</surname>
              <given-names>M</given-names>
            </name>
            <name>
              <surname>Lins</surname>
              <given-names>D</given-names>
            </name>
            <name>
              <surname>Cavalcanti</surname>
              <given-names>N</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>Review Article</subject>
        </subj-group>
      </article-categories>
      <title-group>
        <article-title xml:lang="en">Nutritional interventions in Metabolic Syndrome: a systematic review</article-title>
      </title-group>
      <abstract xml:lang="en">
        <p>There is no consensus on the most appropriate nutritional strategy for treating metabolic syndrome (MS), such that cardiovascular risk is reduced. This study was designed to assess the strength of evidence of the benefits of various nutritional interventions in MS remission. Performed in Medline, Cochrane Library and PubMed databases, the virtual search consisted of randomized clinical trials published between 1999 and 2009 in any language, studies involving individuals aged 18 or older and diagnosed with MS, regardless of the criterion. The Boolean operator and was used in the combination of the MeSH terms "Metabolic Syndrome", "Metabolic x Syndrome" and "Metabolic Syndrome X", the entry terms "Dysmetabolic Syndrome X", Metabolic Cardiovascular Syndrome," "Metabolic X Syndrome" and "Syndrome X, Metabolic", plus the terms "diet", "intervention and diet", "treatment and diet" and "supplementation". For each study included in the review, we estimated the prevalence of MS and the calculation of effectiveness after the follow-up period. Relative risk measures for each study were described by Forest Plot. We identified 131 articles, which, after eligibility criteria, resulted in 15 studies. These studies were divided into four groups: normocaloric diet associated with exercise; isolated normocaloric diet, low-calorie diet combined with exercises; and isolated low-calorie diet. Tests with low-calorie diet associated with exercising revealed higher efficiency values, helping to emphasize the global aspects of lifestyle change in the treatment of MS, in which healthy and low-calorie diet should be complemented with the practice of physical activity.</p>
      </abstract>
      <kwd-group xml:lang="en">
        <kwd>Metabolic syndrome</kwd>
        <kwd>clinical trials</kwd>
        <kwd>exercise</kwd>
        <kwd>diet fat-restricted</kwd>
        <kwd>evidence - based medicine</kwd>
      </kwd-group>
    </front-stub>
    <body>
      <p>
        <bold>REVIEW ARTICLE</bold>
      </p>
      <p>
        <fn id="top-body2">
          <label>
            <bold>Nutritional interventions in Metabolic Syndrome. A systematic review</bold>
          </label>
          <p>
            <bold>Leila Sicupira Carneiro de Souza Le&#227;o; Milena Miranda de Moraes; Giulia Xavier de Carvalho; Rosalina Jorge Koifman</bold>
          </p>
        </fn>
      </p>
      <p>Universidade Federal do Estado do Rio de Janeiro, FIOCRUZ / Escola Nacional de Sa&#250;de P&#250;blica, Rio de Janeiro, RJ - Brasil</p>
      <p>Mailing address</p>
      <p>
        <bold>ABSTRACT</bold>
      </p>
      <p>There is no consensus on the most appropriate nutritional strategy for treating metabolic syndrome (MS), such that cardiovascular risk is reduced. This study was designed to assess the strength of evidence of the benefits of various nutritional interventions in MS remission. Performed in Medline, Cochrane Library and PubMed databases, the virtual search consisted of randomized clinical trials published between 1999 and 2009 in any language, studies involving individuals aged 18 or older and diagnosed with MS, regardless of the criterion. The Boolean operator <italic>and</italic> was used in the combination of the MeSH terms "Metabolic Syndrome", "Metabolic x Syndrome" and "Metabolic Syndrome X", the entry terms "Dysmetabolic Syndrome X", Metabolic Cardiovascular Syndrome," "Metabolic X Syndrome" and "Syndrome X, Metabolic", plus the terms "diet", "intervention and diet", "treatment and diet" and "supplementation". For each study included in the review, we estimated the prevalence of MS and the calculation of effectiveness after the follow-up period. Relative risk measures for each study were described by Forest Plot. We identified 131 articles, which, after eligibility criteria, resulted in 15 studies. These studies were divided into four groups: normocaloric diet associated with exercise; isolated normocaloric diet, low-calorie diet combined with exercises; and isolated low-calorie diet. Tests with low-calorie diet associated with exercising revealed higher efficiency values, helping to emphasize the global aspects of lifestyle change in the treatment of MS, in which healthy and low-calorie diet should be complemented with the practice of physical activity.</p>
      <p><bold>Keywords:</bold> Metabolic syndrome; clinical trials; exercise; diet fat-restricted; evidence - based medicine.</p>
      <p>
        <bold>Introduction </bold>
      </p>
      <p>Metabolic syndrome (MS) is a set of at least three abnormalities, either in blood pressure or metabolism of carbohydrates and lipids, usually associated with cardiovascular disease, the leading cause of morbidity and mortality in Brazil<sup>1</sup>.</p>
      <p>There is no consensus on the most appropriate nutritional strategy to treat MS. Although current proposals related to behavioral alterations such as changed eating habits and physical activity<sup>2</sup>, nutritional recommendations were established from studies with healthy patients or those with isolated metabolic alterations<sup>3-8</sup>. Thus, since the treatment is effective only for one component of the syndrome, instead of diagnosis remission, represented by the normalization of at least three characteristics, cardiovascular protection would therefore be smaller.</p>
      <p>In this context, the Guidelines Project of the Brazilian Society of Endocrinology<sup>4</sup> underscores the need for conducting research that contributes to define the type of intervention that is more effective in the treatment of individuals diagnosed with MS.</p>
      <p>Due to lack of systematic review on this topics, this study was designed to assess the strength of evidence of the benefits of various nutritional interventions in MS remission.</p>
      <p>
        <bold>Methods</bold>
      </p>
      <p>We performed a systematic review of studies with nutritional interventions in individuals with MS diagnosed by the presence of at least three alterations as recommended by the World Health Organization (WHO) in 1999<sup>9</sup>. In addition to this official publication, other diagnostic criteria suggested by the National Cholesterol Education Program - Adult Treatment Panel III (NCEP-ATP III)<sup>10</sup>, American Heart Association (AHA)<sup>11</sup>, International Diabetes Federation (IDF)<sup>12</sup> and European Group for the Study of Insulin Resistance (EGIR) <sup>13</sup> were also considered, as they represented adaptations or modifications of the official criterion.</p>
      <p>The virtual search was performed on Medline, Cochrane Library and PubMed databases, to seek clinical trials published between 1999 and 2009 in any language. The evaluation of eligibility criteria was developed independently by two reviewers; in case of disagreements, advice was asked to a third researcher.</p>
      <p>The Boolean operator <italic>and</italic> was used in the combination of the MeSH terms "Metabolic Syndrome", "Metabolic x Syndrome" and "Metabolic Syndrome X<italic>"</italic>; the entry terms "Dysmetabolic Syndrome X", Metabolic Cardiovascular Syndrome," "Metabolic X Syndrome" and "Syndrome X, Metabolic", plus the terms "diet", "intervention and diet", "treatment and diet" and "supplementation". The type of publication was a randomized clinical trial for all combinations of words.</p>
      <p>Abstracts of selected articles were analyzed to determine whether they met the inclusion criteria which included: presenting a randomized controlled clinical trial proposal for nutritional intervention in population older than 18 years of age, and consider the MS remission as the outcome. We excluded studies of interventions designed to treat only isolated MS alterations.</p>
      <p>Wherever possible, we employed PRISMA<sup>14</sup> to report this systematic review. After reading the full articles, the results were summarized according to the MS diagnosis criterion, nutritional intervention, the control group, the intervention period and the prevalence of MS, the main outcome of this review.</p>
      <p>To make comparison between studies easier, we calculated the effectiveness of interventions through the prevalence values of MS after the follow-up period, applied in the formula proposed by Szklo<sup>15</sup>: { [ (prevalence in the control group - prevalence in the intervention group) / prevalence in the control group] x 100}.</p>
      <p>Relative risk measures for each study were described by Forest Plot, prepared in the statistical software Review Manager, version 5. However, statistical meta-analysis was not justified due to marked heterogeneity of studies included.</p>
      <p>
        <bold>Results</bold>
      </p>
      <p>In the electronic search, 131 publications were obtained, of which, after reading the summaries and excluding some which involved drugs, 59 articles were selected for analysis. After exclusion of 44 articles that did not meet the inclusion criteria, 15 studies were included in the review (<xref ref-type="fig" rid="f1-body2">Figure 1</xref>).</p>
      <fig id="f1-body2">
        <graphic xlink:href="1678-4170-abc-97-03-0260-00012-gf01-en.jpg"/></fig>
      <p>All selected studies were randomized controlled trials and were published in English. As for the location, Italy<sup>16-18</sup> contributed with three studies; the United States<sup>19-23</sup> with five; Finland<sup>24,25</sup> with two; and Japan<sup>26</sup>, Germany<sup>27</sup>, Iran<sup>28</sup>, Spain<sup>29</sup> and Norway<sup>30</sup>, with one each.</p>
      <p>The interventions had periods between six weeks and 31 months and involved 2,089 participants aged between 24 and 75 years with body mass index (BMI) between 26 and 43kg/m<sup>2</sup>. Out of the 15 studies, only three mentioned run in period<sup>16,25,28</sup>, and two with partially blind intervention<sup>17,20</sup>.</p>
      <p>As to the population, four trials studied outpatients from only one hospital<sup>18,22</sup>; two were multicentric<sup>24,29</sup>; two studied population representative of communities<sup>16,30</sup>; three studied patients picked up by newspaper advertisements<sup>19,2526</sup>; one studied university employees<sup>20</sup>; and three did not inform the population studied<sup>21,23,27</sup>.</p>
      <p>The prevalence of MS was the main outcome in six studies<sup>16,24-26,29,30</sup> and secondary when the prevalence of MS components<sup>18-22,27,28</sup>, weight reduction<sup>23</sup> and behavior of inflammatory markers and endothelial function<sup>17</sup> function were the primary outcomes.</p>
      <p>The tests were grouped according to type of intervention, namely: normocaloric diet combined with exercise<sup>16,19</sup>; normocaloric diet<sup>20,29</sup>, low-calorie diet combined with exercise<sup>24,25</sup>, and low-calorie diet<sup>22,27</sup> (<xref ref-type="table" rid="en_12t01-body2">Table 1</xref>).</p>
      <p content-type="asset">
        <table-wrap id="en_12t01-body2">
          <graphic xlink:href="1678-4170-abc-97-03-0260-00012-gt01-en.jpg"/></table-wrap>
      </p>
      <p>
        <bold>Normocaloric diet combined with exercise</bold>
      </p>
      <p>In the study by Stewart et al<sup>16</sup> the intervention group was asked to perform supervised aerobic exercise three times a week, besides the individual diet. Controls received only general guidelines on healthy diet. Similarly, Bo et al<sup>17</sup> instructed its control group with general information, while the intervention group received individualized nutritional counseling and exercise recommendations.</p>
      <p>
        <bold>Normocaloric Diet</bold>
      </p>
      <p>In the study by Mutungi et al<sup>20</sup> the intervention was characterized by a diet without caloric restriction, low-carbohydrate, plus three liquid eggs (Vista<sup>&#174;</sup>) per day. The control group consumed only a maintenance diet. It is noteworthy that although the diet proposal was normocaloric, both groups reduced the energy content of the diet by the end of follow-up period.</p>
      <p>In the trial by Salas-Salvad&#243; et al<sup>29</sup> the two intervention groups consumed a Mediterranean diet supplemented with extra virgin olive oil (1.25L per week) or nuts (15g of walnuts per day; 7.5g of hazelnuts per day; 7.5g of almonds per day). The control group was guided only with normocaloric diet.</p>
      <p>
        <bold>Low-calorie diet combined with exercise</bold>
      </p>
      <p>In the study by Kukkonen Harjula et al<sup>20</sup> participants underwent two phases: one which consisted of weight reduction and another which consisted of weight maintenance with the intervention of interest, diet plus walking, and one control group only with diet. In the study by Villareal et al<sup>21</sup> the intervention consisted of low-calorie diet combined with exercise, while the control group consumed only low-calorie diet. Okura et al<sup>26</sup> provided the control group a low-calorie diet with a food supplement (MicroDiet<sup>&#174;</sup>). The intervention group consumed the same diet associated with exercise.</p>
      <p>In the study by Anderssen et al<sup>30</sup> the group which combined exercise and diet was supervised to perform aerobic activity three times a week and calorie intake with energy restriction. The control group consumed only individualized low-calorie diet.</p>
      <p>In the study by Ilanne-Parikka et al<sup>24</sup> the intervention consisted of guidelines to increase the level of physical activity, addition of 15g of fiber for each 1,000kcal and adoption of a diet low in fat and cholesterol. The control group received only general guidelines.</p>
      <p>
        <bold>Low-calorie diet</bold>
      </p>
      <p>The study by Seshadri et al<sup>22</sup> offered balanced low-calorie diet to the control group, while the intervention group was instructed to consume low-calorie diet low in carbohydrates. Esposito et al<sup>17</sup> oriented the intervention group with a Mediterranean diet, while the control group followed general guidelines on healthy eating.</p>
      <p>In the Azadbakht study<sup>28</sup> the intervention consisted of the DASH diet (Dietary Approaches to Stop Hypertension), with a deficit of 500 kcal/day, higher intake of fruits, vegetables, nonfat dairy foods and lower sodium content.</p>
      <p>Muzio et al<sup>18</sup> conducted intervention with 48% carbohydrates and 65% control, both with a deficit of 500 kcal/day and monthly group sessions for nutritional guidance, while Katcher et al<sup>23</sup> compared a low-calorie diet group based on whole grains with another that consumed refined grains.</p>
      <p>The study by K&#246;nig et al<sup>27</sup> instructed the control group to consume low-calorie diet and the intervention group to replace two meals a day for a soy yogurt with honey (Almased <sup>&#174;</sup>).</p>
      <p>Considering all studies included in the review, as well as the different groups according to type of intervention and corresponding calculation of effectiveness, it was observed that the low-calorie diet combined with physical exercises performed better compared to other groups, followed by normocaloric diet with exercise, isolated low-calorie diet and isolated normocaloric diet.</p>
      <p>However, regardless of the type of nutritional intervention, measures of effect expressed in the Forest Plot describe the protective effect on the risk of developing MS for all proposals for nutritional treatment analyzed (<xref ref-type="fig" rid="en_12f02-body2">Figure 2</xref>).</p>
      <p content-type="asset">
        <fig id="en_12f02-body2">
          <graphic xlink:href="1678-4170-abc-97-03-0260-00012-gf02-en.jpg"/></fig>
      </p>
      <p>
        <bold>Discussion </bold>
      </p>
      <p>As far as it is known, this is the only systematic review to evaluate the evidentiary strength of nutritional interventions in MS diagnosis remission. After an extensive search strategy, inclusion of only 15 studies stated the shortage of literature when it comes to assessing the diagnosis of MS as primary or secondary category-based outcome.</p>
      <p>Besides the quantitative limitation, the low quality and heterogeneity of the studies were also noted. None of the authors conducted the trial according to the CONSORT guide (<ext-link ext-link-type="uri" xlink:href="http://www.consort-statement.org/">http://www.consort-statement.org/</ext-link>); there was high variability in the time of intervention. Some studies stipulated control groups based solely on general guidelines, while others, on calculated diet; and most of them compared groups with small samples (&lt;30 participants).</p>
      <p>These characteristics, associated with poor detailing of the methodology in most articles, prevented clarification on the sample size calculation, as well as specific information about the development of the intervention proposed, such as blinding and run in period, preventing a meta-analysis of the results presented.</p>
      <p>However, the effectiveness of low-calorie proposals combined with physical activity was similar to the interventions performed in individuals with isolated alterations<sup>31-34</sup> and reinforce the suggestion by Reaven<sup>35</sup>, who proposed a low-calorie diet combined with physical activity for the treatment of patients with MS.</p>
      <p>We may consider that reducing diet calorie is the main strategy for the treatment of overweight<sup>36</sup>, because reduced calorie intake promote reduced fat mass by means of negative energy balance, a condition in which energy expenditure exceeds energy intake. When calorie reduction is added to the practice of physical activities, the effect of weight reduction is enhanced, especially in individuals with MS, where the maintenance of lean body mass would increase sensitivity to insulin<sup>37</sup>.</p>
      <p>The importance of physical activity added to a diet plan, though normocaloric, was demonstrated in the studies by Stewart et al<sup>16</sup> and Bo et al<sup>17</sup>. Even with effectiveness inferior results comparing to interventions with low-calorie diet and exercise, similar characteristics of age and BMI in both groups and maintenance of energy consumption after the intervention reinforce the influence of physical activity on weight reduction. At the same time, reduced effectiveness of normocaloric diet not associated with physical activity of Salas-Salvad&#243; et al<sup>19</sup> confirmed the need for a negative energy balance in the treatment of MS, either by reducing calories or by increasing energy expenditure.</p>
      <p>In this sense, we can understand the suggestions by Project Guidelines<sup>4</sup>, who values the need to reduce the energy content of proposed treatments for MS, rather than changes in macronutrient composition. We therefore recommend that high-quality randomized controlled trials be conducted to safely detect the effects of dietary exposures and provide more objective approaches in measuring dietary intake and the outcomes of relevance to public health.</p>
      <p>This systematic review had limitations such as a potential failure to identify all publications despite the attempt to minimize this possibility by applying broad terms, repeating the search in databases and references of selected articles. As strengths, we highlight the systematic approach, the extensive search in relevant databases, inclusion of publications in any language and methodological rigor.</p>
      <p>Although the set of interventions with low-calorie diet combined with physical activity has shown results that stood out among other types of nutritional proposals, the joint analysis of the studies provided evidence of the benefits of individualized diets low in saturated fats, rich in fiber, monounsaturated oils, vitamins and minerals in metabolic syndrome remission.</p>
      <p>
        <bold>Conclusion </bold>
      </p>
      <p>Even taking into account factors that limited this systematic review, it can be concluded that scientific literature supports the beneficial effects of low-calorie diet associated with physical exercise, reinforcing the importance of changing lifestyle in the management of MS.</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 partially funded by UNIRIO and FIOCRUZ.</p>
      <p>
        <bold>Study Association</bold>
      </p>
      <p>This article is part of the thesis of master submitted by Leila Sicupira Carneiro de Souza Le&#227;o, from Escola Nacional de Sa&#250;de P&#250;blica - FIOCRUZ.</p>
      <p>
        <bold>References</bold>
      </p>
    </body>
  </sub-article>
</article>
