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  <front>
    <journal-meta>
      <journal-id journal-id-type="nlm-ta">Arq Bras Cardiol</journal-id>
      <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>
    </journal-meta>
    <article-meta>
      <article-id specific-use="scielo-v3" pub-id-type="publisher-id">c8jsLQfhyjg6xQZ4gPsxMJp</article-id>
      <article-id specific-use="scielo-v2" pub-id-type="publisher-id">S0066-782X2021000600979</article-id>
      <article-id pub-id-type="publisher-id">abc.20210181</article-id>
      <article-id pub-id-type="doi">10.36660/abc.20210181</article-id>
      <article-categories>
        <subj-group subj-group-type="heading">
          <subject>Minieditorial</subject>
        </subj-group>
      </article-categories>
      <title-group>
        <article-title>Suplementa&#231;&#227;o de Vitamina D</article-title>
      </title-group>
      <contrib-group>
        <contrib contrib-type="editor">
          <contrib-id contrib-id-type="orcid">0000-0001-7728-4505</contrib-id>
          <name>
            <surname>Okoshi</surname>
            <given-names>Marina P.</given-names>
          </name>
          <xref ref-type="aff" rid="aff1">
            <sup>1</sup>
          </xref>
          <xref ref-type="corresp" rid="c1"/>
        </contrib>
        <contrib contrib-type="editor">
          <name>
            <surname>Cortez</surname>
            <given-names>Rosana M.</given-names>
          </name>
          <xref ref-type="aff" rid="aff1">
            <sup>1</sup>
          </xref>
          <xref ref-type="aff" rid="aff2">
            <sup>2</sup>
          </xref>
        </contrib>
        <contrib contrib-type="editor">
          <name>
            <surname>Pagan</surname>
            <given-names>Luana U.</given-names>
          </name>
          <xref ref-type="aff" rid="aff1">
            <sup>1</sup>
          </xref>
        </contrib>
        <contrib contrib-type="editor">
          <name>
            <surname>Martinez</surname>
            <given-names>Paula F.</given-names>
          </name>
          <xref ref-type="aff" rid="aff3">
            <sup>3</sup>
          </xref>
        </contrib>
        <contrib contrib-type="editor">
          <name>
            <surname>Pereira</surname>
            <given-names>Filipe W. L.</given-names>
          </name>
          <xref ref-type="aff" rid="aff1">
            <sup>1</sup>
          </xref>
        </contrib>
        <aff id="aff1">
          <label>1</label>
          <institution content-type="orgname">UNESP</institution>
          <institution content-type="orgdiv1">Faculdade de Medicina de Botucatu</institution>
          <institution content-type="orgdiv2">Departamento de Cl&#237;nica M&#233;dica</institution>
          <addr-line>
            <named-content content-type="city">Botucatu</named-content>
            <named-content content-type="state">SP</named-content>
          </addr-line>
          <country country="BR">Brasil</country>
          <institution content-type="original">Departamento de Cl&#237;nica M&#233;dica - Faculdade de Medicina de Botucatu (UNESP), Botucatu, SP - Brasil.</institution>
        </aff>
        <aff id="aff2">
          <label>2</label>
          <institution content-type="orgname">Unimed Sorocaba</institution>
          <addr-line>
            <named-content content-type="city">S&#227;o Paulo</named-content>
            <named-content content-type="state">SP</named-content>
          </addr-line>
          <country country="BR">Brasil</country>
          <institution content-type="original">Unimed Sorocaba, S&#227;o Paulo, SP - Brasil.</institution>
        </aff>
        <aff id="aff3">
          <label>3</label>
          <institution content-type="orgname">Universidade Federal de Mato Grosso do Sul</institution>
          <institution content-type="orgdiv1">Instituto Integrado de Sa&#250;de</institution>
          <addr-line>
            <named-content content-type="city">Campo Grande</named-content>
            <named-content content-type="state">MS</named-content>
          </addr-line>
          <country country="BR">Brasil</country>
          <institution content-type="original">Instituto Integrado de Sa&#250;de, Universidade Federal de Mato Grosso do Sul (UFMS), Campo Grande, MS - Brasil.</institution>
        </aff>
      </contrib-group>
      <author-notes>
        <corresp id="c1"><bold>Correspond&#234;ncia: Marina P. Okoshi</bold> &#8226; Departamento de Cl&#237;nica M&#233;dica, Faculdade de Medicina de Botucatu. Rubi&#227;o Junior, S/N. CEP <postal-code>18618 687</postal-code>, Botucatu, SP &#8211; Brasil. E-mail: <email>mpoliti@fmb.unesp.br</email></corresp>
      </author-notes>
      <pub-date publication-format="electronic" date-type="pub">
        <day>17</day>
        <month>05</month>
        <year>2021</year>
      </pub-date>
      <pub-date publication-format="electronic" date-type="collection">
        <month>05</month>
        <year>2021</year>
      </pub-date>
      <volume>116</volume>
      <issue>5</issue>
      <fpage>979</fpage>
      <lpage>980</lpage>
      <permissions>
        <license license-type="open-access" xml:lang="en" xlink:href="https://creativecommons.org/licenses/by/4.0/">
          <license-p>This is an open-access article distributed under the terms of the Creative Commons Attribution License</license-p>
        </license>
      </permissions>
      <kwd-group xml:lang="pt">
        <title>Palavras-chave</title>
        <kwd>Vitamina D</kwd>
        <kwd>Estado Nutricional</kwd>
        <kwd>Osso e Ossos/metabolismo</kwd>
        <kwd>Suplementos Nutricionais/efeitos adversos</kwd>
      </kwd-group>
      <counts>
        <fig-count count="0"/>
        <table-count count="0"/>
        <equation-count count="0"/>
        <ref-count count="11"/>
        <page-count count="2"/>
      </counts>
    </article-meta>
  </front>
  <body>
    <p>A vitamina D (Vit D) &#233; uma vitamina lipossol&#250;vel essencial para o metabolismo de ossos e minerais. O status de Vit D &#233; avaliado medindo-se os n&#237;veis s&#233;ricos de 25-hidroxivitamina D [25(OH)D]. Atualmente, a suplementa&#231;&#227;o da Vit D &#233; indicada principalmente em casos de defici&#234;ncia. No entanto, existem duas quest&#245;es importantes em rela&#231;&#227;o &#224; suplementa&#231;&#227;o da Vit D. A primeira est&#225; relacionada &#224; defini&#231;&#227;o do limite inferior para os valores considerados normais de [25(OH)D] s&#233;rico. Nos &#250;ltimos anos, extensa pesquisa cl&#237;nica tem revelado que grandes propor&#231;&#245;es das popula&#231;&#245;es globais t&#234;m baixos n&#237;veis de Vit D, isto &#233;, concentra&#231;&#245;es s&#233;ricas de [25(OH)D] menor que 20 ng/mL.<xref ref-type="bibr" rid="B1"><sup>1</sup></xref> Contudo, muitos pesquisadores consideram esse valor superestimado, considerando, assim, que um maior n&#250;mero de pessoas necessitaria de suplementa&#231;&#227;o. Hoje, v&#225;rias sociedades m&#233;dicas est&#227;o em grande discuss&#227;o sobre quando rastrear a defici&#234;ncia de Vit D e quando suplement&#225;-la.<xref ref-type="bibr" rid="B1"><sup>1</sup></xref><sup>,</sup><xref ref-type="bibr" rid="B2"><sup>2</sup></xref></p>
    <p>Outra quest&#227;o a respeito da suplementa&#231;&#227;o da Vit D diz respeito ao fato de que estudos experimentais e epidemiol&#243;gicos convincentes sugerem que a defici&#234;ncia da Vit D esteja associada ao maior risco de doen&#231;as cardiovasculares e doen&#231;as imunes cr&#244;nicas, e c&#226;ncer. Consequentemente, a suplementa&#231;&#227;o da Vit D tem sido realizada na popula&#231;&#227;o geral sem uma indica&#231;&#227;o espec&#237;fica. Contudo, estudos mais recentes t&#234;m relatado que a suplementa&#231;&#227;o da Vit D para a preven&#231;&#227;o ou controle de doen&#231;as cr&#244;nicas como o c&#226;ncer, diabetes mellitus, dem&#234;ncia e doen&#231;as cardiovasculares n&#227;o tem mostrado benef&#237;cios.<xref ref-type="bibr" rid="B3"><sup>3</sup></xref><sup>&#8211;</sup><xref ref-type="bibr" rid="B5"><sup>5</sup></xref> Al&#233;m da aus&#234;ncia de benef&#237;cios, um estudo mostrou que a suplementa&#231;&#227;o di&#225;ria de Vit D foi associada a uma maior necessidade de dispositivos de suporte mec&#226;nico circulat&#243;rio na insufici&#234;ncia card&#237;aca avan&#231;ada, o que indica que &#233; necess&#225;rio cautela em rela&#231;&#227;o &#224; suplementa&#231;&#227;o em longo prazo.<xref ref-type="bibr" rid="B6"><sup>6</sup></xref></p>
    <p>Estudos experimentais s&#227;o importantes, pois permitem estabelecer melhor controle de par&#226;metros envolvidos na suplementa&#231;&#227;o da vitamina.<xref ref-type="bibr" rid="B7"><sup>7</sup></xref><sup>&#8211;</sup><xref ref-type="bibr" rid="B9"><sup>9</sup></xref> Na edi&#231;&#227;o atual dos ABC, Santos et al.<xref ref-type="bibr" rid="B10"><sup>10</sup></xref> confirmaram sua hip&#243;tese de que a suplementa&#231;&#227;o com Vit D em doses que n&#227;o levam &#224; hipercalcemia (doses &#8220;n&#227;o hipercalc&#234;micas&#8221;) induz mudan&#231;as delet&#233;rias no mioc&#225;rdio em ratos, e que esse processo pode, ao menos em parte, ser modulado pela prote&#237;na de intera&#231;&#227;o com a tiorredoxina (TXNIP), pela tiorredoxina (Trx), e pelo estresse oxidativo. Em um elegante estudo, ratos Wistar machos foram submetidos a duas diferentes doses n&#227;o hipercalc&#234;micas por dois meses. A suplementa&#231;&#227;o reduziu a atividade das enzimas envolvidas no metabolismo oxidativo e aumentou a via glicol&#237;tica. O estresse oxidativo foi caracterizado por peroxida&#231;&#227;o lip&#237;dica aumentada e atividade reduzida das enzimas antioxidantes no mioc&#225;rdio dos ratos suplementados. Al&#233;m disso, uma maior express&#227;o da TXNIP e menor atividade da Trx, associadas com redu&#231;&#227;o nos marcadores antiapopt&#243;ticos, foram observados na suplementa&#231;&#227;o com a maior dose de Vit D, de maneira dose-dependente. Considerando o aumento no estresse oxidativo e a diminui&#231;&#227;o nos marcadores antiapopt&#243;ticos, podemos levantar a hip&#243;tese de que, em longo prazo, as altera&#231;&#245;es no mioc&#225;rdio poderiam induzir a remodela&#231;&#227;o card&#237;aca ou predispor cora&#231;&#245;es sadios a efeitos delet&#233;rios da les&#227;o card&#237;aca, tais como isquemia mioc&#225;rdica e hipertens&#227;o arterial. Conforme destacada pelos autores, uma limita&#231;&#227;o do estudo &#233; o curto per&#237;odo de tratamento, o que n&#227;o permitiu determinar se a suplementa&#231;&#227;o cr&#244;nica de Vit D causa remodela&#231;&#227;o card&#237;aca patol&#243;gica.</p>
    <p>Apesar de dados epidemiol&#243;gicas associarem a Vit D a desfechos cardiovasculares, e corroborarem um papel da Vit D no processo patog&#234;nico, dados mecanicistas s&#227;o ainda insuficientes para se recomendar a suplementa&#231;&#227;o da vitamina para preven&#231;&#227;o ou tratamento de outras doen&#231;as que n&#227;o a doen&#231;a &#243;ssea metab&#243;lica.<xref ref-type="bibr" rid="B11"><sup>11</sup></xref></p>
  </body>
  <back>
    <fn-group>
      <fn fn-type="other" id="fn1">
        <p>Minieditorial referente ao artigo: Suplementa&#231;&#227;o de Vitamina D Induz Remodela&#231;&#227;o Card&#237;aca em Ratos: Associa&#231;&#227;o com a Prote&#237;na de Intera&#231;&#227;o com a Tiorredoxina e a Tiorredoxina</p>
      </fn>
    </fn-group>
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  </back>
  <sub-article article-type="translation" id="S01" xml:lang="en">
    <front-stub>
      <article-categories>
        <subj-group subj-group-type="heading">
          <subject>Short Editorial</subject>
        </subj-group>
      </article-categories>
      <title-group>
        <article-title>Supplementation of Vitamin D</article-title>
      </title-group>
      <contrib-group>
        <contrib contrib-type="editor">
          <contrib-id contrib-id-type="orcid">0000-0001-7728-4505</contrib-id>
          <name>
            <surname>Okoshi</surname>
            <given-names>Marina P.</given-names>
          </name>
          <xref ref-type="aff" rid="aff4">
            <sup>1</sup>
          </xref>
          <xref ref-type="corresp" rid="c2"/>
        </contrib>
        <contrib contrib-type="editor">
          <name>
            <surname>Cortez</surname>
            <given-names>Rosana M.</given-names>
          </name>
          <xref ref-type="aff" rid="aff4">
            <sup>1</sup>
          </xref>
          <xref ref-type="aff" rid="aff5">
            <sup>2</sup>
          </xref>
        </contrib>
        <contrib contrib-type="editor">
          <name>
            <surname>Pagan</surname>
            <given-names>Luana U.</given-names>
          </name>
          <xref ref-type="aff" rid="aff4">
            <sup>1</sup>
          </xref>
        </contrib>
        <contrib contrib-type="editor">
          <name>
            <surname>Martinez</surname>
            <given-names>Paula F.</given-names>
          </name>
          <xref ref-type="aff" rid="aff6">
            <sup>3</sup>
          </xref>
        </contrib>
        <contrib contrib-type="editor">
          <name>
            <surname>Pereira</surname>
            <given-names>Filipe W. L.</given-names>
          </name>
          <xref ref-type="aff" rid="aff4">
            <sup>1</sup>
          </xref>
        </contrib>
        <aff id="aff4">
          <label>1</label>
          <addr-line>
            <named-content content-type="city">Botucatu</named-content>
            <named-content content-type="state">SP</named-content>
          </addr-line>
          <country country="BR">Brazil</country>
          <institution content-type="original">Departamento de Cl&#237;nica M&#233;dica - Faculdade de Medicina de Botucatu (UNESP), Botucatu, SP - Brazil.</institution>
        </aff>
        <aff id="aff5">
          <label>2</label>
          <addr-line>
            <named-content content-type="city">S&#227;o Paulo</named-content>
            <named-content content-type="state">SP</named-content>
          </addr-line>
          <country country="BR">Brazil</country>
          <institution content-type="original">Unimed Sorocaba, S&#227;o Paulo, SP - Brazil.</institution>
        </aff>
        <aff id="aff6">
          <label>3</label>
          <addr-line>
            <named-content content-type="city">Campo Grande</named-content>
            <named-content content-type="state">MS</named-content>
          </addr-line>
          <country country="BR">Brazil</country>
          <institution content-type="original">Instituto Integrado de Sa&#250;de, Universidade Federal de Mato Grosso do Sul (UFMS), Campo Grande, MS - Brazil.</institution>
        </aff>
      </contrib-group>
      <author-notes>
        <corresp id="c2"><bold>Mailing Address: Marina P. Okoshi</bold> &#8226; Departamento de Cl&#237;nica M&#233;dica, Faculdade de Medicina de Botucatu. Rubi&#227;o Junior, S/N. Postal Code <postal-code>18618 687</postal-code>, Botucatu, SP &#8211; Brazil. E-mail: <email>mpoliti@fmb.unesp.br</email></corresp>
      </author-notes>
      <kwd-group xml:lang="en">
        <title>Keywords</title>
        <kwd>Vitamin D</kwd>
        <kwd>Nutritional Status</kwd>
        <kwd>Bone and Bones/metabolism</kwd>
        <kwd>Dietary Supplements/adverse effects</kwd>
      </kwd-group>
    </front-stub>
    <body>
      <p>Vitamin D (Vit D) is a fat-soluble vitamin that is essential in mineral and bone metabolism. Vit D status is evaluated by measuring serum 25-hydroxyvitamin D [25(OH)D]) levels. Currently, Vit D supplementation is mainly indicated in cases of vitamin deficiency. However, there are two main issues concerning Vit D supplementation. The first is related to the definition of the lower limit of normal for serum 25(OH) D. In recent years, extensive clinical research has revealed that large percentages of global populations have low Vit D levels, i.e., serum [25(OH)D] concentrations below 20 ng/mL.<xref ref-type="bibr" rid="B1"><sup>1</sup></xref> However, several investigators have considered that this value is probably overestimated, therefore putting more people in need for supplementation. Several medical societies are now intensively debating on when to screen for Vit D deficiency and when to supplement Vit D.<xref ref-type="bibr" rid="B1"><sup>1</sup></xref><sup>,</sup><xref ref-type="bibr" rid="B2"><sup>2</sup></xref></p>
      <p>The other issue concerning Vit D supplementation relates to the fact that convincing experimental and epidemiological studies have suggested that Vit D deficiency is associated with increased risk of chronic cardiovascular and immunological diseases and cancer. Therefore, Vit D has been supplemented in the general population without a specific indication. However, more recent studies have reported that Vit D supplementation for preventing or controlling chronic diseases such as cancer, diabetes mellitus, dementia or cardiovascular disease has failed to provide benefits.<xref ref-type="bibr" rid="B3"><sup>3</sup></xref><sup>&#8211;</sup><xref ref-type="bibr" rid="B5"><sup>5</sup></xref> Furthermore, not only were no benefits found. In advanced heart failure, a daily Vit D supplement was associated with a greater need for mechanical circulatory support devices, which indicates caution regarding long-term supplementation.<xref ref-type="bibr" rid="B6"><sup>6</sup></xref></p>
      <p>Experimental studies are important as they allow the establishment of better control parameters involved in vitamin supplementation.<xref ref-type="bibr" rid="B7"><sup>7</sup></xref><sup>&#8211;</sup><xref ref-type="bibr" rid="B9"><sup>9</sup></xref> In the current issue of ABC, Santos et al.<xref ref-type="bibr" rid="B10"><sup>10</sup></xref> confirmed their hypotheses that Vit D supplementation at non-hypercalcemic doses induces detrimental myocardial changes in rats and that this process may, at least in part, be modulated by thioredoxin-interacting protein (TXNIP), thioredoxin (Trx), and oxidative stress. In an elegant study, male Wistar rats were subjected to two different non-hypercalcemic Vit D doses for two months. Supplementation decreased the activity of enzymes involved in oxidative metabolism and increased the glycolytic pathway. Increased oxidative stress was characterized by higher lipid peroxidation and reduced antioxidant enzyme activity in myocardium of the supplemented rats. Additionally, higher TXNIP expression and lower Trx activity, associated with reduced antiapoptotic markers, were also observed with the higher dose of Vit D, in a dose-dependent manner. Considering the increased oxidative stress and reduced antiapoptotic markers, we can hypothesize that in the long-term the myocardial changes could induce cardiac remodeling or predispose healthy hearts to deleterious effects of cardiac injury, such as myocardial ischemia and arterial hypertension. As pointed out by the authors, one limitation of the study is the short treatment period, which did not allow to determine whether chronic Vit D supplementation causes pathological cardiac remodeling.</p>
      <p>Although epidemiological data link Vit D to cardiovascular outcomes and support a role for Vit D in pathogenic processes, mechanistic data are insufficient to recommend Vit D supplementation for prevention or treatment of diseases other than bone metabolic disease.<xref ref-type="bibr" rid="B11"><sup>11</sup></xref></p>
    </body>
    <back>
      <fn-group>
        <fn fn-type="other" id="fn2">
          <p>Short Editorial related to the article: Vitamin D Supplementation Induces Cardiac Remodeling in Rats: Association with Thioredoxin-Interacting Protein and Thioredoxin</p>
        </fn>
      </fn-group>
    </back>
  </sub-article>
</article>
