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<front>
<journal-meta>
<journal-id journal-id-type="publisher-id">Front. Vet. Sci.</journal-id>
<journal-title>Frontiers in Veterinary Science</journal-title>
<abbrev-journal-title abbrev-type="pubmed">Front. Vet. Sci.</abbrev-journal-title>
<issn pub-type="epub">2297-1769</issn>
<publisher>
<publisher-name>Frontiers Media S.A.</publisher-name>
</publisher>
</journal-meta>
<article-meta>
<article-id pub-id-type="doi">10.3389/fvets.2023.1227500</article-id>
<article-categories>
<subj-group subj-group-type="heading">
<subject>Veterinary Science</subject>
<subj-group>
<subject>General Commentary</subject>
</subj-group>
</subj-group>
</article-categories>
<title-group>
<article-title>Commentary: Invited review: glucosinolates might result in low methane emissions from ruminants fed brassica forages</article-title>
</title-group>
<contrib-group>
<contrib contrib-type="author" corresp="yes" equal-contrib="yes">
<name><surname>Todini</surname> <given-names>Luca</given-names></name>
<xref ref-type="corresp" rid="c001"><sup>&#x0002A;</sup></xref>
<xref ref-type="author-notes" rid="fn001"><sup>&#x02020;</sup></xref>
<uri xlink:href="http://loop.frontiersin.org/people/2321716/overview"/>
</contrib>
<contrib contrib-type="author" equal-contrib="yes">
<name><surname>Fantuz</surname> <given-names>Francesco</given-names></name>
<xref ref-type="author-notes" rid="fn001"><sup>&#x02020;</sup></xref>
</contrib>
</contrib-group>
<aff><institution>School of Biosciences and Veterinary Medicine, University of Camerino</institution>, <addr-line>Matelica</addr-line>, <country>Italy</country></aff>
<author-notes>
<fn fn-type="edited-by"><p>Edited by: Nazir Ahmad Khan, University of Agriculture, Pakistan</p></fn>
<fn fn-type="edited-by"><p>Reviewed by: Juan Keim, Universidad Austral de Chile, Chile</p></fn>
<corresp id="c001">&#x0002A;Correspondence: Luca Todini <email>luca.todini&#x00040;unicam.it</email></corresp>
<fn fn-type="equal" id="fn001"><p>&#x02020;These authors have contributed equally to this work and share first authorship</p></fn></author-notes>
<pub-date pub-type="epub">
<day>06</day>
<month>10</month>
<year>2023</year>
</pub-date>
<pub-date pub-type="collection">
<year>2023</year>
</pub-date>
<volume>10</volume>
<elocation-id>1227500</elocation-id>
<history>
<date date-type="received">
<day>23</day>
<month>05</month>
<year>2023</year>
</date>
<date date-type="accepted">
<day>18</day>
<month>09</month>
<year>2023</year>
</date>
</history>
<permissions>
<copyright-statement>Copyright &#x000A9; 2023 Todini and Fantuz.</copyright-statement>
<copyright-year>2023</copyright-year>
<copyright-holder>Todini and Fantuz</copyright-holder>
<license xlink:href="http://creativecommons.org/licenses/by/4.0/"><p>This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.</p></license>
</permissions>
<related-article id="RA1" related-article-type="commentary-article" journal-id="Front. Vet. Sci." journal-id-type="nlm-ta" vol="7" page="588051" xlink:href="33195622" ext-link-type="pubmed">A Commentary on <article-title>Invited review: glucosinolates might result in low methane emissions from ruminants fed brassica forages</article-title> by Sun, X. (2020) <italic>Front. Vet. Sci</italic>. 7:588051. doi: <object-id>10.3389/fvets.2020.588051</object-id></related-article>
<kwd-group>
<kwd>Digesta Retention Time</kwd>
<kwd>free triiodothyronine</kwd>
<kwd>greenhouse gas</kwd>
<kwd>physiological parameters</kwd>
<kwd>plant secondary compounds</kwd>
<kwd>rumen</kwd>
</kwd-group>
<counts>
<fig-count count="0"/>
<table-count count="0"/>
<equation-count count="0"/>
<ref-count count="15"/>
<page-count count="3"/>
<word-count count="1852"/>
</counts>
<custom-meta-wrap>
<custom-meta>
<meta-name>section-at-acceptance</meta-name>
<meta-value>Animal Nutrition and Metabolism</meta-value>
</custom-meta>
</custom-meta-wrap>
</article-meta>
</front>
<body>
<sec sec-type="intro" id="s1">
<title>Introduction</title>
<p>The present commentary aims to clarify some main physiological concepts and literature findings that may be subject to confusion arising from the invited review (<xref ref-type="bibr" rid="B1">1</xref>) (referred to as &#x0201C;TIR&#x0201D; hereafter), published in 2020 in this journal <italic>Frontiers in Veterinary Science</italic>.</p>
<p>The purpose of TIR was &#x0201C;to summarize literature reports on the use of brassica forage to mitigate CH<sub>4</sub> emissions &#x02026; and highlight the possible role of glucosinolates&#x0201D;. The articles quoted in TIR indicate that &#x0201C;ruminants fed forage brassica emit low methane&#x0201D;, and that &#x0201C;a shorter mean retention time of particulate and liquid digesta is associated with less CH<sub>4</sub> yield&#x0201D;.</p>
<p>Then, the &#x0201C;Effects of Secondary Metabolites in Brassica Forages on Triiodothyronine&#x0201D; and &#x0201C;The effects of Free Triiodothyronine on Digesta Retention Time and on Methane Emissions&#x0201D; are reviewed.</p>
</sec>
<sec id="s2">
<title>Literature cited</title>
<p>Several concerns arise when TIR faces &#x0201C;Effects of Secondary Metabolites in Brassica Forages on Triiodothyronine&#x0201D;. The topic of Brassicas, glucosinolates (GLS), and thyroid function is challenging, and the related literature is really extensive. The present Commentary considers articles cited by TIR, and we believe that certain results from these articles have not been adequately considered, leading to an unsupported hypothesis.</p>
<p>First, TIR states that &#x0201C;S-methyl-L-cysteine sulfoxide can increase ghrelin and thyroid hormones in the plasma (12)&#x0201D;. However, in that cited review (<xref ref-type="bibr" rid="B2">2</xref>), it is stated that &#x0201C;kale feeding is associated with increased blood plasma concentrations of growth hormone and thyroxine&#x0201D; (not ghrelin and thyroid hormones). This sentence refers to previous experiments by the same author [(<xref ref-type="bibr" rid="B3">3</xref>, <xref ref-type="bibr" rid="B4">4</xref>); the latter is not cited by TIR], comparing diets (kale vs. ryegrass-clover pasture) and iodine supplementation (with vs. without). In the presence of supplementary iodine (&#x0201C;to counteract the goitrogenic properties of the inorganic thiocyanate ion released on hydrolysis of GLS&#x0201D;), kale feeding was associated with an elevation in the plasma concentration of T<sub>4</sub>. When iodine supplementation compensated for the anti-thyroidal actions of GLS, S-methyl-L-cysteine sulfoxide (SMCO) was hypothesized to have a stimulatory effect on T<sub>4</sub> increase. However, to the best of our knowledge, this hypothesis was not further investigated. It should be noted that T<sub>3</sub> (triiodothyronine) remained unaffected by the diet. As stated in TIR, &#x0201C;it is unlikely that SMCO has an effect on blood FT<sub>3</sub> concentration&#x0201D;. When growing lambs were fed kale without iodine supplementation, concentrations of both thyroid hormones (TH) dropped (less markedly for T<sub>3</sub>), as expected and reported (<xref ref-type="bibr" rid="B4">4</xref>).</p>
<p>Comparably, serum T<sub>4</sub> concentrations decreased in lambs grazing Brassicas, which were restored by iodine supplementation (<xref ref-type="bibr" rid="B5">5</xref>). Again, serum T<sub>3</sub> levels remained unaffected by the diets (<xref ref-type="bibr" rid="B5">5</xref>). Unfortunately, the citation of this latter article in TIR appears to be non-compliant, as it states that &#x0201C;For example, feeding turnip (<italic>Brassica rapa</italic> L.) and kale (<italic>B. oleracea</italic> L. var. <italic>acephala</italic> DC) to fattening lambs can increase the concentrations of T<sub>3</sub> and T<sub>4</sub> in serum (76)&#x0201D;.</p>
<p>Similar findings were observed in calves fed rapeseed&#x02013;mustard cakes with high or low GLS contents (<xref ref-type="bibr" rid="B6">6</xref>): &#x0201C;T<sub>3</sub> remained within the normal range&#x0201D;, while T<sub>4</sub> decreased in a dose-dependent manner. Unfortunately, these results, reported in the original article as &#x0201C;thyroxine changed quadratically with increasing glucosinolate levels&#x0201D;, were reported in TIR as &#x0201C;quadratically increased serum T<sub>4</sub> concentration&#x0201D;.</p>
<p>Goitrogenic effects of GSL, and therefore their ability to decrease T<sub>4</sub> secretion by the gland and TH blood concentrations, are widely confirmed by the literature cited in TIR, involving pigs (<xref ref-type="bibr" rid="B7">7</xref>), mares (<xref ref-type="bibr" rid="B8">8</xref>), turkeys (<xref ref-type="bibr" rid="B9">9</xref>), and sheep (<xref ref-type="bibr" rid="B10">10</xref>, <xref ref-type="bibr" rid="B11">11</xref>).</p>
<p>Among the references mentioned in TIR, only the abstract is available for (<xref ref-type="bibr" rid="B12">12</xref>), stating that &#x0201C;The sheep receiving GLS and nitrates without iodine and selenium supplementation developed enlargement of the thyroid gland, &#x02026; low T<sub>4</sub> level&#x02026;, high T<sub>3</sub> level and a narrow T<sub>3</sub>/T<sub>4</sub> ratio&#x0201D;. The full text of (<xref ref-type="bibr" rid="B13">13</xref>), dealing with rats, is not available.</p>
</sec>
<sec sec-type="discussion" id="s3">
<title>Discussion</title>
<p>The thyroid gland primarily secretes T<sub>4</sub>, making blood T<sub>4</sub> concentrations indicative of the synthesizing and secretory rates of the gland. On the other hand, T<sub>3</sub> secretion by the thyroid gland is minimal, and the majority of circulating T<sub>3</sub> is derived from the activation of T<sub>4</sub> to T<sub>3</sub> by deiodinase enzymes at the peripheral level. Therefore, circulating T<sub>3</sub> concentrations reflect the rate of deiodinase activity, representing the balance between peripheral enzymes involved in activating and inactivating T<sub>4</sub>.</p>
<p>The data from articles cited by TIR are consistent with basic physiological knowledge regarding the effects of GLS and iodine on thyroid gland activity and TH blood concentrations. It has been well-established for decades that GLS derivatives inhibit TH synthesis and secretion, interfering with various steps of the process in a dose-dependent manner. The main effects involve the inhibition of the thyroperoxidase (TPO) enzyme, leading to the impairment of iodide uptake, oxidation, binding to thyroglobulin, and hormone secretion. Moreover, such goitrogenic compounds interfere with the deiodination of T<sub>4</sub> in peripheral tissues. Many literature articles on various species have reported that iodine supplementation can at least partially restore physiological functions and parameters, including circulating TH, impaired by GLS intake.</p>
<p>Among mammals, ruminants are less sensitive to these effects than monogastric species due to greater degradation of the active compounds in the forestomach environment. Regarding the effects on blood TH concentrations and T3/T4 ratio, it is important to consider the quality and amounts of Brassica forages included in the diets (and iodine intake, as well). Recently, in dairy cows, no effect was found on T3 replacing 25% of DM with Brassicas (<xref ref-type="bibr" rid="B14">14</xref>), nor on T3 and T4 with 30 and 45% forage rape (<xref ref-type="bibr" rid="B15">15</xref>).</p>
<p>In conclusion, literature data are often contradictory and do not seem to support the hypotheses proposed in TIR (&#x0201C;GSLs and/or their breakdown products in brassica forage crops &#x02026; increase blood FT<sub>3</sub> concentration in ruminants&#x0201D;). Furthermore, the &#x0201C;Concluding remarks&#x0201D; (&#x0201C;GSL and its metabolites can elevate the concentration of FT<sub>3</sub> in ruminants&#x0201D;) and the &#x0201C;Abstract&#x0201D; (&#x0201C;It is reported that feeding brassica forages to sheep can increase the concentration of free triiodothyronine (FT<sub>3</sub>) in serum. We hypothesize that GSLs or their breakdown products may stimulate the secretion of thyroid hormone FT<sub>3</sub> in ruminants&#x0201D;) is not substantiated by the cited references. Finally, in Figure 4, the first step of the diagram appears to lack support from the references cited.</p>
</sec>
<sec sec-type="author-contributions" id="s4">
<title>Author contributions</title>
<p>All authors listed have made a substantial, direct, and intellectual contribution to the work and approved it for publication.</p>
</sec>
</body>
<back>
<sec sec-type="funding-information" id="s5">
<title>Funding</title>
<p>Publication fees are granted by unspecified funds of LT (FAR/LT/BVI000023unicam).</p>
</sec>
<sec sec-type="COI-statement" id="conf1">
<title>Conflict of interest</title>
<p>The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.</p>
</sec>
<sec sec-type="disclaimer" id="s6">
<title>Publisher&#x00027;s note</title>
<p>All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.</p>
</sec>
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