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<front>
<journal-meta>
<journal-id journal-id-type="publisher-id">Front. Nutr.</journal-id>
<journal-title>Frontiers in Nutrition</journal-title>
<abbrev-journal-title abbrev-type="pubmed">Front. Nutr.</abbrev-journal-title>
<issn pub-type="epub">2296-861X</issn>
<publisher>
<publisher-name>Frontiers Media S.A.</publisher-name>
</publisher>
</journal-meta>
<article-meta>
<article-id pub-id-type="doi">10.3389/fnut.2024.1376508</article-id>
<article-categories>
<subj-group subj-group-type="heading">
<subject>Nutrition</subject>
<subj-group>
<subject>Systematic Review</subject>
</subj-group>
</subj-group>
</article-categories>
<title-group>
<article-title>Do polyphenols affect body fat and/or glucose metabolism?</article-title>
</title-group>
<contrib-group>
<contrib contrib-type="author" corresp="yes">
<name><surname>Alqarni</surname> <given-names>Saleha</given-names></name>
<xref ref-type="aff" rid="aff1"><sup>1</sup></xref>
<xref ref-type="corresp" rid="c001"><sup>&#x002A;</sup></xref>
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</contrib>
<contrib contrib-type="author">
<name><surname>Alsebai</surname> <given-names>Mashael</given-names></name>
<xref ref-type="aff" rid="aff2"><sup>2</sup></xref>
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</contrib>
<contrib contrib-type="author">
<name><surname>Alsaigh</surname> <given-names>Batool Adal</given-names></name>
<xref ref-type="aff" rid="aff1"><sup>1</sup></xref>
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</contrib>
<contrib contrib-type="author">
<name><surname>Alrashedy</surname> <given-names>Abeer Sayer</given-names></name>
<xref ref-type="aff" rid="aff1"><sup>1</sup></xref>
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<contrib contrib-type="author">
<name><surname>Albahrani</surname> <given-names>Israa Talal</given-names></name>
<xref ref-type="aff" rid="aff1"><sup>1</sup></xref>
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<contrib contrib-type="author">
<name><surname>Aljohar</surname> <given-names>Albandri Yousef</given-names></name>
<xref ref-type="aff" rid="aff1"><sup>1</sup></xref>
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<contrib contrib-type="author">
<name><surname>Alazmi</surname> <given-names>Amjad Obaid</given-names></name>
<xref ref-type="aff" rid="aff1"><sup>1</sup></xref>
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<aff id="aff1"><sup>1</sup><institution>Department of Clinical Nutrition, College of Applied Medical Science, King Faisal University</institution>, <addr-line>Al-Ahsa</addr-line>, <country>Saudi Arabia</country></aff>
<aff id="aff2"><sup>2</sup><institution>Department of Clinical Nutrition, Nottingham University</institution>, <addr-line>Nottingham</addr-line>, <country>United Kingdom</country></aff>
<author-notes>
<fn fn-type="edited-by" id="fn0001">
<p>Edited by: Alessandra Durazzo, Council for Agricultural Research and Economics, Italy</p>
</fn>
<fn fn-type="edited-by" id="fn0002">
<p>Reviewed by: Claudia Ivette Gamboa, Mexican Social Security Institute, Mexico</p>
<p>Yongsheng Chen, Jinan University, China</p>
</fn>
<corresp id="c001">&#x002A;Correspondence: Saleha Alqarni, <email>saleha.alqarni@outlook.sa</email></corresp>
</author-notes>
<pub-date pub-type="epub">
<day>11</day>
<month>06</month>
<year>2024</year>
</pub-date>
<pub-date pub-type="collection">
<year>2024</year>
</pub-date>
<volume>11</volume>
<elocation-id>1376508</elocation-id>
<history>
<date date-type="received">
<day>25</day>
<month>01</month>
<year>2024</year>
</date>
<date date-type="accepted">
<day>17</day>
<month>05</month>
<year>2024</year>
</date>
</history>
<permissions>
<copyright-statement>Copyright &#x00A9; 2024 Alqarni, Alsebai, Alsaigh, Alrashedy, Albahrani, Aljohar and Alazmi.</copyright-statement>
<copyright-year>2024</copyright-year>
<copyright-holder>Alqarni, Alsebai, Alsaigh, Alrashedy, Albahrani, Aljohar and Alazmi</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>
<abstract>
<sec id="sec1">
<title>Background</title>
<p>Obesity is reaching epidemic proportions with 51% of the population expected to be obese by 2030. Recently, polyphenols have been highlighted as an effective approach to managing obesity and associated risks. Polyphenols are a large class of bioactive plant compounds classified into two major categories: flavonoids which are distinguished by the fundamental C6-C3-C6 skeleton and non-flavonoids.</p>
</sec>
<sec id="sec2">
<title>Objective</title>
<p>This systematic review evaluated the effect of different polyphenol sources in overweight and obese people with and without type 2 diabetes. The primary outcome was lipid profile and the secondary outcomes were blood glucose, HbA1c (%), HOMA-IR, weight, and body mass index.</p>
</sec>
<sec id="sec3">
<title>Method</title>
<p>A search was undertaken in PubMed, Web of Science, Medline, and Wiley for randomized control trials that assessed different sources of polyphenols in overweight and obese people with or without type 2 diabetes. The quality of the included studies was assessed using the National Heart, Lung, and Blood Institute Quality Assessment Tool.</p>
</sec>
<sec id="sec4">
<title>Result</title>
<p>The search yielded 935 studies, of which six randomized control trials met the inclusion criteria. Five studies found no significant difference in lipid profile between the control and intervention groups in triglycerides, total cholesterol, LDL cholesterol, and HDL cholesterol. However, one study showed significant differences in triglycerides (<italic>p</italic>&#x2009;=&#x2009;0.04) and HDL cholesterol (<italic>p</italic>&#x2009;=&#x2009;0.05) between the two groups with no significant difference in total cholesterol and LDL cholesterol. There were no significant changes in blood glucose observed in the included studies, with only two studies reporting a significant difference in A1c between the groups. Four studies found no difference in HOMA-IR, while one study showed a significant decrease in HOMA-IR in the intervention group compared to the control group. Three studies reported no difference in BMI or weight between the two groups.</p>
</sec>
<sec id="sec5">
<title>Conclusion</title>
<p>The data associated with the specific health benefits of polyphenols and their sources in people with overweight, obese, and type 2 diabetes are still limited, so further research is required to support their use and prove their benefits.</p>
</sec>
</abstract>
<kwd-group>
<kwd>polyphenols</kwd>
<kwd>antioxidants</kwd>
<kwd>type 2 diabetes</kwd>
<kwd>obesity</kwd>
<kwd>lipid</kwd>
</kwd-group>
<counts>
<fig-count count="2"/>
<table-count count="5"/>
<equation-count count="0"/>
<ref-count count="62"/>
<page-count count="12"/>
<word-count count="7110"/>
</counts>
<custom-meta-wrap>
<custom-meta>
<meta-name>section-at-acceptance</meta-name>
<meta-value>Clinical Nutrition</meta-value>
</custom-meta>
</custom-meta-wrap>
</article-meta>
</front>
<body>
<sec sec-type="intro" id="sec6">
<title>Introduction</title>
<p>Obesity has reached epidemic proportions, with the World Health Organization (WHO) estimating that there are more than 1.9 billion overweight adults worldwide, of which 650 million are obese (<xref ref-type="bibr" rid="ref1">1</xref>). In addition, there are more than 340 million overweight or obese children and adolescents between the ages of 5 and 19 (<xref ref-type="bibr" rid="ref1">1</xref>). By 2030, 51% of the population is expected to be obese (<xref ref-type="bibr" rid="ref2">2</xref>). Excess weight is associated with a range of metabolic complications such as hypertension, insulin resistance, dyslipidaemia, and type 2 diabetes (<xref ref-type="bibr" rid="ref3 ref4 ref5">3&#x2013;5</xref>), as well as a significant economic burden. The direct costs include healthcare costs for treating related diseases, while indirect costs include lost productivity due to disability or premature death (<xref ref-type="bibr" rid="ref2">2</xref>, <xref ref-type="bibr" rid="ref6">6</xref>). Altering lifestyles to reduce calorie consumption and increase physical activity are difficult to preserve in the long term, therefore, it is necessary to find methods to lower the prevalence of obesity and its associated diseases.</p>
<p>Recently, polyphenols have been highlighted as a practical approach to managing obesity and associated risks. Polyphenols are an enormous class of bioactive plant compounds classified into two major categories: flavonoids which are distinguished by the fundamental C6-C3-C6 skeleton, and non-flavonoids (particularly phenolic acids, stilbenes, and lignans) (<xref ref-type="bibr" rid="ref7">7</xref>) as shown in <xref ref-type="table" rid="tab1">Table 1</xref>. Flavones, flavonols, isoflavones, flavanones, anthocyanins, and flavanols, commonly known as catechins, are the subclasses that result from the heterocyclic ring connecting the two aromatic rings (<xref ref-type="bibr" rid="ref7">7</xref>), the primary forms are either conjugated with acid-alcohol or with glycosides in plant food items (<xref ref-type="bibr" rid="ref7">7</xref>, <xref ref-type="bibr" rid="ref8">8</xref>). In addition, polyphenols exist as monomers and oligomers, which are typically referred to as tannins (<xref ref-type="bibr" rid="ref8">8</xref>). Condensed tannins and hydrolysable tannins are derived from catechin and are usually called procyanidins (<xref ref-type="bibr" rid="ref8">8</xref>). Phenolic compounds are challenging to quantify because of their diversity and complexity (<xref ref-type="bibr" rid="ref7">7</xref>, <xref ref-type="bibr" rid="ref8">8</xref>). As Polyphenols represent a diverse group of phytochemicals found abundantly in plant-based foods as shown in <xref ref-type="table" rid="tab1">Table 1</xref>.</p>
<table-wrap position="float" id="tab1">
<label>Table 1</label>
<caption>
<p>Classes of polyphenols and the principal dietary constituents.</p>
</caption>
<table frame="hsides" rules="groups">
<thead>
<tr>
<th align="left" valign="top">Class</th>
<th align="left" valign="top">Sub-class</th>
<th align="left" valign="top">Dietary sources</th>
</tr>
</thead>
<tbody>
<tr>
<td align="left" valign="top" rowspan="5">Flavonoids</td>
<td align="left" valign="top">Flavones</td>
<td align="left" valign="top">Plants and spices like thyme, rosemary, oregano, and parsley<break/>Fruits: celery and olives<break/>Vegetables: hot peppers and celery hearts</td>
</tr>
<tr>
<td align="left" valign="top">Isoflavones</td>
<td align="left" valign="top">Grape seed/skin<break/>Soybean, soy nuts, soy flour/bread, tofu, miso, soy milk, and tofu yoghurt are among the products made from legumes</td>
</tr>
<tr>
<td align="left" valign="top">Anthocyanidins</td>
<td align="left" valign="top">Elderberries, strawberries, cherries, plums, cranberries, blackberries, black currants, blueberries, black grapes, blackberries, blackberries, and pomegranate juice</td>
</tr>
<tr>
<td align="left" valign="top">Flavanones</td>
<td align="left" valign="top">Lemon, lime orange, orange, grapefruit, tangerine, peppermint</td>
</tr>
<tr>
<td align="left" valign="top">Flavanols</td>
<td align="left" valign="top">Apples, apricots, grapes, peaches, nectarines, pears, plums, raisins, raspberries, cherries, blackberries, blues, and cranberries<break/>White wine, black tea, dark chocolate, green tea, and cacao</td>
</tr>
<tr>
<td align="left" valign="top" rowspan="4">Non-flavonoids</td>
<td align="left" valign="top">Stilbenes</td>
<td align="left" valign="top">Grapes, rhubarb and peanuts</td>
</tr>
<tr>
<td align="left" valign="top">Lignans</td>
<td align="left" valign="top">Nuts, seeds, rye, wheat, oats, barley, soybean, apricots and strawberries, broccoli, cabbage</td>
</tr>
<tr>
<td align="left" valign="top">Hydroxybenzoic acids</td>
<td align="left" valign="top">Strawberries, raspberries, grape juice (black/green) pomegranate juice</td>
</tr>
<tr>
<td align="left" valign="top">Hydroxycinnamic acids</td>
<td align="left" valign="top">Tea, coffee, spinach, potato, lettuce, orange, grapefruit, cherry juice, apple juice, lemon, peach, cranberry, pear, cherry (sweet), apple, orange, grapefruit, pear juice, and cider</td>
</tr>
</tbody>
</table>
</table-wrap>
<sec id="sec7">
<title>Flavonoids</title>
<p>This subgroup constitutes the largest and most studied class of polyphenols. Flavonoids are further categorized into subclasses such as flavonols, flavones, flavanones, flavan-3-ols (including catechins), anthocyanins, and isoflavones. They are found in fruits, vegetables, tea, wine, and various herbal remedies (<xref ref-type="bibr" rid="ref9">9</xref>, <xref ref-type="bibr" rid="ref10">10</xref>).</p>
</sec>
<sec id="sec8">
<title>Phenolic acids</title>
<p>These are aromatic compounds found in various plant foods, particularly in fruits (e.g., berries), vegetables, whole grains, and beverages like coffee. Major subclasses include hydroxybenzoic acids (e.g., gallic acid) and hydroxycinnamic acids (e.g., caffeic acid, ferulic acid) (<xref ref-type="bibr" rid="ref9">9</xref>, <xref ref-type="bibr" rid="ref11">11</xref>).</p>
</sec>
<sec id="sec9">
<title>Lignans</title>
<p>Lignans are polyphenolic compounds abundant in seeds, whole grains, fruits, and vegetables. They are converted by intestinal bacteria into enterolignans, which have been associated with various health benefits, including hormone regulation and antioxidant activity (<xref ref-type="bibr" rid="ref9">9</xref>, <xref ref-type="bibr" rid="ref11">11</xref>).</p>
</sec>
<sec id="sec10">
<title>Stilbenes</title>
<p>This subgroup includes compounds such as resveratrol, primarily found in grapes, red wine, peanuts, and berries. Resveratrol has gained attention for its potential health-promoting effects, including anti-inflammatory and cardioprotective properties (<xref ref-type="bibr" rid="ref9">9</xref>, <xref ref-type="bibr" rid="ref11">11</xref>).</p>
</sec>
<sec id="sec11">
<title>Others</title>
<p>This category encompasses a wide range of polyphenolic compounds, including tannins, stilbenoids, and curcuminoids. Tannins are commonly found in tea, wine, and certain fruits, and they contribute to the astringent taste of these foods. Stilbenoids, besides resveratrol, include pterostilbene, found in blueberries and grapes (<xref ref-type="bibr" rid="ref9">9</xref>, <xref ref-type="bibr" rid="ref11">11</xref>). Curcuminoids are derived from turmeric and exhibit various biological activities, including antioxidant and anti-inflammatory properties.</p>
<p>There are several possible mechanisms for the positive effect of polyphenols in obesity and associated risks as shown in <xref ref-type="fig" rid="fig1">Figure 1</xref> including the inhibition of fat absorption from the gastrointestinal tract, glucose uptake by skeletal muscles, the regulation of fat production, appetite suppression, the modulation of the gut microbiota, and reduced chronic inflammation associated with obesity (<xref ref-type="bibr" rid="ref12">12</xref>, <xref ref-type="bibr" rid="ref13">13</xref>).</p>
<fig position="float" id="fig1">
<label>Figure 1</label>
<caption>
<p>Polyphenols mechanisms.</p>
</caption>
<graphic xlink:href="fnut-11-1376508-g001.tif"/>
</fig>
<p>Numerous epidemiological and clinical studies have investigated the effect of different polyphenols on obesity and associated risks. For example, Shrime et al. (<xref ref-type="bibr" rid="ref14">14</xref>), revealed that consuming cocoa, which is high in flavanol, reduced insulin resistance. Also, insulin resistance was improved in healthy individuals who consumed pure-epicatechin for a month by alterations in fasting insulin levels without affecting fasting glucose levels (<xref ref-type="bibr" rid="ref15">15</xref>). In a systematic analysis of six studies, the green coffee extract reduced fasting blood glucose, while only larger dosages helped enhance insulin resistance (<xref ref-type="bibr" rid="ref16">16</xref>). Following a 12-week olive leaf polyphenols supplementation in middle-aged, overweight men had increased insulin action and secretion (<xref ref-type="bibr" rid="ref17">17</xref>). A systematic review and meta-analysis of six studies reported that pistachio nut consumption enhanced insulin resistance (<xref ref-type="bibr" rid="ref18">18</xref>). Pecan and almond eating appear to improve insulin resistance (<xref ref-type="bibr" rid="ref19">19</xref>, <xref ref-type="bibr" rid="ref20">20</xref>). However, a systematic review of walnuts found no impact on fasting blood glucose or other measures of insulin resistance (<xref ref-type="bibr" rid="ref21">21</xref>).</p>
<p>Habitual consumption of tea was linked to lower body fat in a cross-sectional human study in Taiwan (<xref ref-type="bibr" rid="ref22">22</xref>). In addition, a longitudinal investigation from the Netherlands showed a lower body mass index among women with higher dietary flavone, flavonol, and catechin consumption (<xref ref-type="bibr" rid="ref23">23</xref>). Furthermore, clinical trials have shown a positive effect of high doses of catechins in tea drinks, effectively reducing body fat and body weight, especially when combined with an exercise regimen (<xref ref-type="bibr" rid="ref24">24</xref>, <xref ref-type="bibr" rid="ref25">25</xref>). Moreover, a recent meta-analysis showed that consuming resveratrol significantly reduces weight, body mass index, and fat mass (<xref ref-type="bibr" rid="ref26">26</xref>). However, a systematic review and meta-analysis of 19 RCTs focusing on the effect of anthocyanin on cardiometabolic biomarkers showed that there is no significant effect of anthocyanin supplementation on body mass index, body weight, waist circumference, and blood pressure (<xref ref-type="bibr" rid="ref27">27</xref>).</p>
<p>Inconsistencies in the findings and methodological limitations of individual studies, as well as inconsistencies in the results of previous systematic reviews and meta-analyses, justify the need for a comprehensive systematic review to assess the impact of polyphenols on obesity and its associated risks. In contrast to previous systematic reviews, different types of polyphenols were included and compared. In addition to the increasing volume of new studies, an updated systematic review is needed. Therefore, this systematic review compared different sources of polyphenols in overweight and obese individuals with or without type 2 diabetes. The primary outcome was lipid profile and the secondary outcomes were blood glucose, HbA1c (%), HOMA-IR, weight, and body mass index.</p>
</sec>
</sec>
<sec sec-type="methods" id="sec12">
<title>Methodology</title>
<p>This systematic review was conducted according to The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist (<xref ref-type="bibr" rid="ref28">28</xref>).</p>
<sec id="sec13">
<title>Search strategy</title>
<p>A systematic search of the PubMed, Web of Science, Medline and Wiley databases was performed from 13th May 2023 to Jane 2023 using the following terms: &#x201C;(&#x201C;resveratrol (3,5,4&#x2019;trihydroxystilbene)&#x201D; OR &#x201C;epigallocatechin 3 gallate&#x201D; OR &#x201C;epigallocatechin gallate (ECG)&#x201D; OR &#x201C;epigallocatechin&#x201D; OR &#x201C;quercetin&#x201D; OR &#x201C;flavonoids&#x201D; OR &#x201C;Polyphenols&#x201D; OR &#x201C;tannins&#x201D; OR &#x201C;lignans&#x201D; OR &#x201C;stilbenes&#x201D; OR &#x201C;green tea catechins&#x201D; OR &#x201C;catechins&#x201D; OR &#x201C;epicatechin&#x201D; OR &#x201C;procyanidin&#x201D; OR &#x201C;genistein&#x201D; OR &#x201C;provinols&#x201D; OR &#x201C;phenolic acids&#x201D; OR &#x201C;apigenin&#x201D; OR &#x201C;blackberry polyphenols&#x201D; OR &#x201C;curcumin&#x201D; OR &#x201C;grape polyphenols&#x201D; OR &#x201C;cranberry polyphenols&#x201D; OR &#x201C;strawberry polyphenols&#x201D;) AND (&#x201C;insulin resistant&#x201D; OR &#x201C;insulin receptor substrate&#x201D; OR &#x201C;insulin receptor pathway&#x201D; OR &#x201C;GLUT&#x201D; OR&#x201C;insulin sensitivity&#x201D;) AND (&#x201C;Lipid&#x201D; OR &#x201C;HDL&#x201D; OR &#x201C;LDL&#x201D; OR &#x201C;Total cholesterol&#x201D; OR &#x201C;Triglycerides&#x201D;) AND (&#x201C;fat accumulation&#x201D; OR &#x201C;obesity&#x201D; OR &#x201C;overweight&#x201D; OR &#x201C;hyperlipidemia&#x201D; AND &#x201C;glucose&#x201D; OR &#x201C;blood sugar&#x201D;) AND (&#x201C;clinical trial&#x201D;). In addition to manual search in references list. All identified studies were saved in EndNote and duplicates were removed.</p>
<p>The criterion for selecting the types of foods presented in the search terms was based on their known richness in polyphenols, as documented in scientific literature. We considered foods that are commonly recognized for their high polyphenol content and relevance to human consumption. Additionally, we aimed to include a diverse range of food sources to provide a comprehensive overview of polyphenol intake. However, there are many other sources of polyphenol not included in our search terms, including olives oil and that should be considered in future research.</p>
</sec>
<sec id="sec14">
<title>Eligibility criteria</title>
<p>The current systematic review examined study eligibility using a population comparison and outcome as shown in <xref ref-type="table" rid="tab2">Table 2</xref>:</p><list list-type="bullet">
<list-item>
<p>Study design: randomized control trial to address the research question</p>
</list-item>
<list-item>
<p>Population: Overweight and obese adults with or without type 2 diabetes</p>
</list-item>
<list-item>
<p>Intervention: different sources of polyphenols</p>
</list-item>
<list-item>
<p>Outcomes: The primary outcome is lipid profile and secondary outcomes are blood glucose, HbA1c (%), weight and body mass index.</p>
</list-item>
</list>
<table-wrap position="float" id="tab2">
<label>Table 2</label>
<caption>
<p>Population&#x2013;intervention&#x2013;comparison&#x2013;outcome (PICOS) criteria for study inclusion and exclusion.</p>
</caption>
<table frame="hsides" rules="groups">
<thead>
<tr>
<th align="left" valign="top">Criteria category</th>
<th align="left" valign="top">Inclusion</th>
<th align="left" valign="top">Exclusion</th>
</tr>
</thead>
<tbody>
<tr>
<td align="left" valign="top">Population</td>
<td align="left" valign="top">Overweight and obese adults with or without type 2 diabetes</td>
<td align="left" valign="top">Normal weight adults<break/>Children/animals</td>
</tr>
<tr>
<td align="left" valign="top">Intervention</td>
<td align="left" valign="top">Polyphenols</td>
<td align="left" valign="top">The intervention is not polyphenols</td>
</tr>
<tr>
<td align="left" valign="top">Comparators</td>
<td align="left" valign="top">Overweight and obese adults with or without type 2 diabetes not treated with polyphenols</td>
<td align="left" valign="top">Normal weight adults<break/>Children/animals</td>
</tr>
<tr>
<td align="left" valign="top">Outcome measure</td>
<td align="left" valign="top">Primary outcome is lipid profile and secondary outcomes are blood glucose, HbA1c (%), HOMA-IR, weight and body mass index</td>
<td align="left" valign="top">Lipid profile not assessed</td>
</tr>
<tr>
<td align="left" valign="top">Study design</td>
<td align="left" valign="top">Randomised control trials</td>
<td align="left" valign="top">Observational studies, review studies, case reports, pilot studies</td>
</tr>
</tbody>
</table>
</table-wrap>
</sec>
<sec id="sec15">
<title>Exclusion criteria</title>
<p>
<list list-type="bullet">
<list-item>
<p>Review studies</p>
</list-item>
<list-item>
<p>Case reports</p>
</list-item>
<list-item>
<p>Observation study</p>
</list-item>
<list-item>
<p>Non-English studies</p>
</list-item>
<list-item>
<p>The full text of the study was not available.</p>
</list-item>
</list>
</p>
</sec>
<sec id="sec16">
<title>Data extraction and synthesis</title>
<p>The following data were extracted from the studies: the author&#x2019;s name, the year of publication, the study location, the study design, the target population, the sample size, the baseline characteristics of participants, and the primary outcome lipid profile. The secondary outcomes were blood glucose, weight, and body mass index. A meta-analysis was not performed due to the heterogeneity of the data.</p>
</sec>
<sec id="sec17">
<title>Quality assessment</title>
<p>The study quality was evaluated using the National Heart, Lung, and Blood Institute (NHLBI) Quality Assessment Tool for randomized controlled trials (<xref ref-type="bibr" rid="ref29">29</xref>). The tool comprises 14 questions answered using the following options: yes, no, not reported, or not applicable.</p>
</sec>
</sec>
<sec sec-type="results" id="sec18">
<title>Results</title>
<sec id="sec19">
<title>Eligibility of studies</title>
<p>The literature search retrieved 935 studies, of which 97 were duplicate studies. Further screening of the title and abstract led to the exclusion of 811 studies, leaving 27 studies to be assessed against the inclusion/exclusion criteria and finally, six studies were included in this review (<xref ref-type="fig" rid="fig2">Figure 2</xref>).</p>
<fig position="float" id="fig2">
<label>Figure 2</label>
<caption>
<p>Stages of selecting studies.</p>
</caption>
<graphic xlink:href="fnut-11-1376508-g002.tif"/>
</fig>
</sec>
<sec id="sec20">
<title>Quality assessment</title>
<p>The quality of each study was evaluated using the NHLBI Quality Assessment Tool for randomized controlled trials (<xref ref-type="table" rid="tab3">Table 3</xref>). Overall, the studies reported on the effect of different sources of polyphenols in overweight and obese people with and without type 2 diabetes seem convergent and reliable to indicate the effect of polyphenols.</p>
<table-wrap position="float" id="tab3">
<label>Table 3</label>
<caption>
<p>NHLBI tool for quality assessment of included studies.</p>
</caption>
<table frame="hsides" rules="groups">
<thead>
<tr>
<th/>
<th align="left" valign="top">Criteria</th>
<th align="center" valign="top">Kirch et al. (<xref ref-type="bibr" rid="ref30">30</xref>)</th>
<th align="center" valign="top">Paquette et al. (<xref ref-type="bibr" rid="ref31">31</xref>)</th>
<th align="center" valign="top">Stendell-Hollis et al. (<xref ref-type="bibr" rid="ref32">32</xref>)</th>
<th align="center" valign="top">Woerdeman et al. (<xref ref-type="bibr" rid="ref33">33</xref>)</th>
<th align="center" valign="top">Aghasi et al. (<xref ref-type="bibr" rid="ref34">34</xref>)</th>
<th align="center" valign="top">Asadi et al. (<xref ref-type="bibr" rid="ref35">35</xref>)</th>
</tr>
</thead>
<tbody>
<tr>
<td align="left" valign="top">1.</td>
<td align="left" valign="top">Was the study described as randomised, a randomised trial, a randomised clinical trial, or an RCT?</td>
<td align="center" valign="top">
<inline-graphic xlink:href="fnut-11-1376508-i001.tif"/>
</td>
<td align="center" valign="top">
<inline-graphic xlink:href="fnut-11-1376508-i001.tif"/>
</td>
<td align="center" valign="top">
<inline-graphic xlink:href="fnut-11-1376508-i001.tif"/>
</td>
<td align="center" valign="top">
<inline-graphic xlink:href="fnut-11-1376508-i001.tif"/>
</td>
<td align="center" valign="top">
<inline-graphic xlink:href="fnut-11-1376508-i001.tif"/>
</td>
<td align="center" valign="top">
<inline-graphic xlink:href="fnut-11-1376508-i001.tif"/>
</td>
</tr>
<tr>
<td align="left" valign="top">2.</td>
<td align="left" valign="top">Was the method of randomization adequate (i.e., use of randomly generated assignment)?</td>
<td align="center" valign="top">
<inline-graphic xlink:href="fnut-11-1376508-i001.tif"/>
</td>
<td align="center" valign="top">
<inline-graphic xlink:href="fnut-11-1376508-i001.tif"/>
</td>
<td align="center" valign="top">
<inline-graphic xlink:href="fnut-11-1376508-i001.tif"/>
</td>
<td align="center" valign="top">
<inline-graphic xlink:href="fnut-11-1376508-i001.tif"/>
</td>
<td align="center" valign="top">
<inline-graphic xlink:href="fnut-11-1376508-i001.tif"/>
</td>
<td align="center" valign="top">
<inline-graphic xlink:href="fnut-11-1376508-i001.tif"/>
</td>
</tr>
<tr>
<td align="left" valign="top">3.</td>
<td align="left" valign="top">Was the treatment allocation concealed (so that assignments could not be predicted)?</td>
<td align="center" valign="top">
<inline-graphic xlink:href="fnut-11-1376508-i001.tif"/>
</td>
<td align="center" valign="top">
<inline-graphic xlink:href="fnut-11-1376508-i001.tif"/>
</td>
<td align="center" valign="top">
<inline-graphic xlink:href="fnut-11-1376508-i001.tif"/>
</td>
<td align="center" valign="top">
<inline-graphic xlink:href="fnut-11-1376508-i001.tif"/>
</td>
<td align="center" valign="top">
<inline-graphic xlink:href="fnut-11-1376508-i001.tif"/>
</td>
<td align="center" valign="top">
<inline-graphic xlink:href="fnut-11-1376508-i001.tif"/>
</td>
</tr>
<tr>
<td align="left" valign="top">4.</td>
<td align="left" valign="top">Were study participants and providers blinded to treatment group assignment?</td>
<td align="center" valign="top">
<inline-graphic xlink:href="fnut-11-1376508-i001.tif"/>
</td>
<td align="center" valign="top">
<inline-graphic xlink:href="fnut-11-1376508-i001.tif"/>
</td>
<td align="center" valign="top">
<inline-graphic xlink:href="fnut-11-1376508-i001.tif"/>
</td>
<td align="center" valign="top">
<inline-graphic xlink:href="fnut-11-1376508-i001.tif"/>
</td>
<td align="center" valign="top">
<inline-graphic xlink:href="fnut-11-1376508-i001.tif"/>
</td>
<td align="center" valign="top">
<inline-graphic xlink:href="fnut-11-1376508-i001.tif"/>
</td>
</tr>
<tr>
<td align="left" valign="top">5.</td>
<td align="left" valign="top">Were the people assessing the outcomes blinded to the participants&#x2019; group assignments?</td>
<td align="center" valign="top">
<inline-graphic xlink:href="fnut-11-1376508-i001.tif"/>
</td>
<td align="center" valign="top">
<inline-graphic xlink:href="fnut-11-1376508-i001.tif"/>
</td>
<td align="center" valign="top">
<inline-graphic xlink:href="fnut-11-1376508-i001.tif"/>
</td>
<td align="center" valign="top">
<inline-graphic xlink:href="fnut-11-1376508-i001.tif"/>
</td>
<td align="center" valign="top">
<inline-graphic xlink:href="fnut-11-1376508-i001.tif"/>
</td>
<td align="center" valign="top">
<inline-graphic xlink:href="fnut-11-1376508-i001.tif"/>
</td>
</tr>
<tr>
<td align="left" valign="top">6.</td>
<td align="left" valign="top">Were the groups similar at baseline on important characteristics that could affect outcomes (e.g., demographics, risk factors, co-morbid conditions)?</td>
<td align="center" valign="top">
<inline-graphic xlink:href="fnut-11-1376508-i001.tif"/>
</td>
<td align="center" valign="top">
<inline-graphic xlink:href="fnut-11-1376508-i001.tif"/>
</td>
<td align="center" valign="top">
<inline-graphic xlink:href="fnut-11-1376508-i001.tif"/>
</td>
<td align="center" valign="top">
<inline-graphic xlink:href="fnut-11-1376508-i001.tif"/>
</td>
<td align="center" valign="top">
<inline-graphic xlink:href="fnut-11-1376508-i001.tif"/>
</td>
<td align="center" valign="top">
<inline-graphic xlink:href="fnut-11-1376508-i001.tif"/>
</td>
</tr>
<tr>
<td align="left" valign="top">7.</td>
<td align="left" valign="top">Was the overall drop-out rate from the study at endpoint 20% or lower of the number allocated to treatment?</td>
<td align="center" valign="top">
<inline-graphic xlink:href="fnut-11-1376508-i001.tif"/>
</td>
<td align="center" valign="top">
<inline-graphic xlink:href="fnut-11-1376508-i001.tif"/>
</td>
<td align="center" valign="top">
<inline-graphic xlink:href="fnut-11-1376508-i002.tif"/>
</td>
<td align="center" valign="top">
<inline-graphic xlink:href="fnut-11-1376508-i001.tif"/>
</td>
<td align="center" valign="top">
<inline-graphic xlink:href="fnut-11-1376508-i001.tif"/>
</td>
<td align="center" valign="top">
<inline-graphic xlink:href="fnut-11-1376508-i001.tif"/>
</td>
</tr>
<tr>
<td align="left" valign="top">8.</td>
<td align="left" valign="top">Was the differential drop-out rate (between treatment groups) at endpoint 15 percentage points or lower?</td>
<td align="center" valign="top">
<inline-graphic xlink:href="fnut-11-1376508-i001.tif"/>
</td>
<td align="center" valign="top">
<inline-graphic xlink:href="fnut-11-1376508-i001.tif"/>
</td>
<td align="center" valign="top">
<inline-graphic xlink:href="fnut-11-1376508-i002.tif"/>
</td>
<td align="center" valign="top">
<inline-graphic xlink:href="fnut-11-1376508-i001.tif"/>
</td>
<td align="center" valign="top">
<inline-graphic xlink:href="fnut-11-1376508-i001.tif"/>
</td>
<td align="center" valign="top">
<inline-graphic xlink:href="fnut-11-1376508-i001.tif"/>
</td>
</tr>
<tr>
<td align="left" valign="top">9.</td>
<td align="left" valign="top">9. Was there high adherence to the intervention protocols for each treatment group?</td>
<td align="center" valign="top">
<inline-graphic xlink:href="fnut-11-1376508-i001.tif"/>
</td>
<td align="center" valign="top">
<inline-graphic xlink:href="fnut-11-1376508-i001.tif"/>
</td>
<td align="center" valign="top">
<inline-graphic xlink:href="fnut-11-1376508-i002.tif"/>
</td>
<td align="center" valign="top">
<inline-graphic xlink:href="fnut-11-1376508-i001.tif"/>
</td>
<td align="center" valign="top">
<inline-graphic xlink:href="fnut-11-1376508-i001.tif"/>
</td>
<td align="center" valign="top">
<inline-graphic xlink:href="fnut-11-1376508-i001.tif"/>
</td>
</tr>
<tr>
<td align="left" valign="top">10.</td>
<td align="left" valign="top">Were other interventions avoided or similar in the groups (e.g., similar background treatments)?</td>
<td align="center" valign="top">
<inline-graphic xlink:href="fnut-11-1376508-i001.tif"/>
</td>
<td align="center" valign="top">
<inline-graphic xlink:href="fnut-11-1376508-i001.tif"/>
</td>
<td align="center" valign="top">
<inline-graphic xlink:href="fnut-11-1376508-i001.tif"/>
</td>
<td align="center" valign="top">
<inline-graphic xlink:href="fnut-11-1376508-i001.tif"/>
</td>
<td align="center" valign="top">
<inline-graphic xlink:href="fnut-11-1376508-i001.tif"/>
</td>
<td align="center" valign="top">
<inline-graphic xlink:href="fnut-11-1376508-i001.tif"/>
</td>
</tr>
<tr>
<td align="left" valign="top">11.</td>
<td align="left" valign="top">Were outcomes assessed using valid and reliable measures, implemented consistently across all study participants?</td>
<td align="center" valign="top">
<inline-graphic xlink:href="fnut-11-1376508-i001.tif"/>
</td>
<td align="center" valign="top">
<inline-graphic xlink:href="fnut-11-1376508-i001.tif"/>
</td>
<td align="center" valign="top">
<inline-graphic xlink:href="fnut-11-1376508-i001.tif"/>
</td>
<td align="center" valign="top">
<inline-graphic xlink:href="fnut-11-1376508-i001.tif"/>
</td>
<td align="center" valign="top">
<inline-graphic xlink:href="fnut-11-1376508-i001.tif"/>
</td>
<td align="center" valign="top">
<inline-graphic xlink:href="fnut-11-1376508-i001.tif"/>
</td>
</tr>
<tr>
<td align="left" valign="top">12.</td>
<td align="left" valign="top">Did the authors report that the sample size was sufficiently large to be able to detect a difference in the main outcome between groups with at least 80% power?</td>
<td align="center" valign="top">
<inline-graphic xlink:href="fnut-11-1376508-i003.tif"/>
</td>
<td align="center" valign="top">
<inline-graphic xlink:href="fnut-11-1376508-i003.tif"/>
</td>
<td align="center" valign="top">
<inline-graphic xlink:href="fnut-11-1376508-i003.tif"/>
</td>
<td align="center" valign="top">
<inline-graphic xlink:href="fnut-11-1376508-i003.tif"/>
</td>
<td align="center" valign="top">
<inline-graphic xlink:href="fnut-11-1376508-i003.tif"/>
</td>
<td align="center" valign="top">
<inline-graphic xlink:href="fnut-11-1376508-i003.tif"/>
</td>
</tr>
<tr>
<td align="left" valign="top">13.</td>
<td align="left" valign="top">Were outcomes reported or subgroups analyzed prespecified (i.e., identified before analyses were conducted)?</td>
<td align="center" valign="top">
<inline-graphic xlink:href="fnut-11-1376508-i001.tif"/>
</td>
<td align="center" valign="top">
<inline-graphic xlink:href="fnut-11-1376508-i001.tif"/>
</td>
<td align="center" valign="top">
<inline-graphic xlink:href="fnut-11-1376508-i001.tif"/>
</td>
<td align="center" valign="top">
<inline-graphic xlink:href="fnut-11-1376508-i001.tif"/>
</td>
<td align="center" valign="top">
<inline-graphic xlink:href="fnut-11-1376508-i001.tif"/>
</td>
<td align="center" valign="top">
<inline-graphic xlink:href="fnut-11-1376508-i001.tif"/>
</td>
</tr>
<tr>
<td align="left" valign="top">14.</td>
<td align="left" valign="top">Were all randomszed participants analysed in the group to which they were originally assigned, i.e., did they use an intention-to-treat analysis?</td>
<td align="center" valign="top">
<inline-graphic xlink:href="fnut-11-1376508-i001.tif"/>
</td>
<td align="center" valign="top">
<inline-graphic xlink:href="fnut-11-1376508-i001.tif"/>
</td>
<td align="center" valign="top">
<inline-graphic xlink:href="fnut-11-1376508-i001.tif"/>
</td>
<td align="center" valign="top">
<inline-graphic xlink:href="fnut-11-1376508-i001.tif"/>
</td>
<td align="center" valign="top">
<inline-graphic xlink:href="fnut-11-1376508-i001.tif"/>
</td>
<td align="center" valign="top">
<inline-graphic xlink:href="fnut-11-1376508-i001.tif"/>
</td>
</tr>
</tbody>
</table>
<table-wrap-foot>
<p><inline-graphic xlink:href="fnut-11-1376508-i001.tif"/>+, yes; <inline-graphic xlink:href="fnut-11-1376508-i002.tif"/><inline-formula>
<mml:math id="M1">
<mml:mo>&#x2212;</mml:mo>
</mml:math>
</inline-formula>, no; <inline-graphic xlink:href="fnut-11-1376508-i003.tif"/>?, cannot determine; <inline-graphic xlink:href="fnut-11-1376508-i004.tif"/>a, not applicable; <inline-graphic xlink:href="fnut-11-1376508-i005.tif"/>r, not reported.</p>
</table-wrap-foot>
</table-wrap>
</sec>
<sec id="sec21">
<title>Study characteristics</title>
<p>The six included studies, which involved a total of 301 adults, were published between 2010 and 2019. Four studies were conducted on people who were obese or overweight (<xref ref-type="bibr" rid="ref30 ref31 ref32 ref33">30&#x2013;33</xref>), and two studies were conducted on people with type 2 diabetes (<xref ref-type="bibr" rid="ref34">34</xref>, <xref ref-type="bibr" rid="ref35">35</xref>).</p>
<p>Different sources of polyphenols were assessed including epicatechin (<xref ref-type="bibr" rid="ref30">30</xref>), strawberry and cranberry (<xref ref-type="bibr" rid="ref31">31</xref>), green tea (<xref ref-type="bibr" rid="ref32">32</xref>), red wine (<xref ref-type="bibr" rid="ref33">33</xref>), green cardamom (<xref ref-type="bibr" rid="ref34">34</xref>), and <italic>Melissa officinalis</italic> (<xref ref-type="bibr" rid="ref35">35</xref>). The study characteristics and results are shown in <xref ref-type="table" rid="tab4">Tables 4</xref>, <xref ref-type="table" rid="tab5">5</xref>.</p>
<table-wrap position="float" id="tab4">
<label>Table 4</label>
<caption>
<p>Obesity and polyphenols.</p>
</caption>
<table frame="hsides" rules="groups">
<thead>
<tr>
<th align="center" valign="top" colspan="7">Obesity and polyphenols</th>
</tr>
<tr>
<th align="left" valign="top">Authors, year</th>
<th align="left" valign="top">Study design</th>
<th align="left" valign="top">Location</th>
<th align="left" valign="top">Interventions vs. control</th>
<th align="left" valign="top">Baseline characteristics of the participants</th>
<th align="left" valign="top">Post treatment characteristics of the participants</th>
<th align="left" valign="top">Results<break/><italic>p</italic>-value</th>
</tr>
</thead>
<tbody>
<tr>
<td align="left" valign="top" rowspan="2">Kirch et al. (<xref ref-type="bibr" rid="ref30">30</xref>)</td>
<td align="left" valign="top" rowspan="2">RCT</td>
<td align="left" valign="top" rowspan="2">Germany</td>
<td align="left" valign="top">Intervention (<italic>n</italic>)&#x2009;=&#x2009;23<break/>25&#x2009;mg-epicatechin<break/>for 2&#x2009;weeks</td>
<td align="left" valign="top">Wt&#x2009;=&#x2009;103.0&#x2009;&#x00B1;&#x2009;3.8<break/>BMI&#x2009;=&#x2009;32.8&#x2009;&#x00B1;&#x2009;0.8<break/>Triglycerides&#x2009;=&#x2009;2.22&#x2009;&#x00B1;&#x2009;0.19<break/>Total cholesterol&#x2009;=&#x2009;5.92&#x2009;&#x00B1;&#x2009;0.14<break/>LDL cholesterol&#x2009;=&#x2009;3.80&#x2009;&#x00B1;&#x2009;0.12<break/>HDL cholesterol&#x2009;=&#x2009;1.35&#x2009;&#x00B1;&#x2009;0.06<break/>HOMA-IR&#x2009;=&#x2009;2.83 (2.00, 4.27)<break/>Glucose&#x2009;=&#x2009;5.72 (5.38, 6.00)</td>
<td align="left" valign="top">Wt&#x2009;=&#x2009;102.8&#x2009;&#x00B1;&#x2009;3.8<break/>BMI&#x2009;=&#x2009;32.7&#x2009;&#x00B1;&#x2009;0.8<break/>Triglycerides&#x2009;=&#x2009;2.231&#x2009;&#x00B1;&#x2009;0.27<break/>Total cholesterol&#x2009;=&#x2009;5.73&#x2009;&#x00B1;&#x2009;0.15<break/>LDL cholesterol&#x2009;=&#x2009;3.76&#x2009;&#x00B1;&#x2009;0.13<break/>HDL cholesterol&#x2009;=&#x2009;1.28&#x2009;&#x00B1;&#x2009;0.06<break/>HOMA-IR&#x2009;=&#x2009;2.88 (1.90, 4.39)<break/>Glucose&#x2009;=&#x2009;5.61 (5.22, 6.11)</td>
<td align="left" valign="top" rowspan="2">Daily intake of 25&#x2009;mg of pure (&#x2212;)-epicatechin for 2 wk. does not reduce cardiometabolic risk factors in overweight-to-obese adults (<italic>p</italic> &#x003E;&#x2009;0.5). There were no significant changes in the parameters of glucose metabolism (glucose, HOMA-IR).</td>
</tr>
<tr>
<td align="left" valign="top">Control (<italic>n</italic>)&#x2009;=&#x2009;24<break/>Placebo for 2&#x2009;weeks</td>
<td align="left" valign="top">Wt&#x2009;=&#x2009;103.2&#x2009;&#x00B1;&#x2009;3.8<break/>BMI&#x2009;=&#x2009;32.8&#x2009;&#x00B1;&#x2009;0.8<break/>Triglycerides&#x2009;=&#x2009;2.11&#x2009;&#x00B1;&#x2009;0.17<break/>Total cholesterol&#x2009;=&#x2009;5.94&#x2009;&#x00B1;&#x2009;0.14<break/>LDL cholesterol&#x2009;=&#x2009;3.86&#x2009;&#x00B1;&#x2009;0.11<break/>HDL cholesterol&#x2009;=&#x2009;1.33&#x2009;&#x00B1;&#x2009;0.06<break/>HOMA-IR&#x2009;=&#x2009;2.86 (1.93, 4.15)<break/>Glucose&#x2009;=&#x2009;5.66 (5.33, 6.11)</td>
<td align="left" valign="top">Wt&#x2009;=&#x2009;102.9&#x2009;&#x00B1;&#x2009;3.7<break/>BMI&#x2009;=&#x2009;32.8&#x2009;&#x00B1;&#x2009;0.8<break/>Triglycerides&#x2009;=&#x2009;2.24&#x2009;&#x00B1;&#x2009;0.19<break/>Total cholesterol&#x2009;=&#x2009;5.71&#x2009;&#x00B1;&#x2009;0.16<break/>LDL cholesterol&#x2009;=&#x2009;3.68&#x2009;&#x00B1;&#x2009;0.12<break/>HDL cholesterol&#x2009;=&#x2009;1.30&#x2009;&#x00B1;&#x2009;0.06<break/>HOMA-IR&#x2009;=&#x2009;2.94 (1.82, 4.08)<break/>Glucose&#x2009;=&#x2009;5.55 (5.27, 6.11)</td>
</tr>
<tr>
<td align="left" valign="top" rowspan="2">Paquette et al. (<xref ref-type="bibr" rid="ref31">31</xref>)</td>
<td align="left" valign="top" rowspan="2">RCT</td>
<td align="left" valign="top" rowspan="2">Canada</td>
<td align="left" valign="top">Intervention (<italic>n</italic>)&#x2009;=&#x2009;20<break/>333&#x2009;mg strawberry and cranberry polyphenols beverage /day for 6&#x2009;weeks</td>
<td align="left" valign="top">Wt&#x2009;=&#x2009;85&#x2009;&#x00B1;&#x2009;3<break/>BMI&#x2009;=&#x2009;31&#x2009;&#x00B1;&#x2009;1<break/>Triglycerides&#x2009;=&#x2009;2.03&#x2009;&#x00B1;&#x2009;0.24<break/>Total cholesterol&#x2009;=&#x2009;5.70&#x2009;&#x00B1;&#x2009;0.17<break/>LDL cholesterol&#x2009;=&#x2009;3.52&#x2009;&#x00B1;&#x2009;0.17<break/>HDL cholesterol&#x2009;=&#x2009;1.25&#x2009;&#x00B1;&#x2009;0.05</td>
<td align="left" valign="top">Wt&#x2009;=&#x2009;&#x2212;<break/>BMI&#x2009;=&#x2009;&#x2212;<break/>Triglycerides&#x2009;=&#x2009;1.82&#x2009;&#x00B1;&#x2009;0.21<break/>Total cholesterol&#x2009;=&#x2009;5.60&#x2009;&#x00B1;&#x2009;0.19<break/>LDL cholesterol&#x2009;=&#x2009;3.51&#x2009;&#x00B1;&#x2009;0.17<break/>HDL cholesterol&#x2009;=&#x2009;1.26&#x2009;&#x00B1;&#x2009;0.06</td>
<td align="left" valign="top" rowspan="2">No differences in changes from baseline (Post v. Pre) for total, LDL- and HDL-cholesterol or TAG were observed within each group or between the two groups</td>
</tr>
<tr>
<td align="left" valign="top">Control (<italic>n</italic>)&#x2009;=&#x2009;21<break/>Placebo for 6&#x2009;weeks</td>
<td align="left" valign="top">Wt&#x2009;=&#x2009;85&#x2009;&#x00B1;&#x2009;3<break/>BMI&#x2009;=&#x2009;31&#x2009;&#x00B1;&#x2009;1<break/>Triglycerides&#x2009;=&#x2009;1.73&#x2009;&#x00B1;&#x2009;0.26<break/>Total cholesterol&#x2009;=&#x2009;5.37&#x2009;&#x00B1;&#x2009;0.22<break/>LDL cholesterol&#x2009;=&#x2009;3.20&#x2009;&#x00B1;&#x2009;0.15<break/>HDL cholesterol&#x2009;=&#x2009;1.33&#x2009;&#x00B1;&#x2009;0.05</td>
<td align="left" valign="top">Wt&#x2009;=&#x2009;&#x2212;<break/>BMI&#x2009;=&#x2009;&#x2212;<break/>Triglycerides&#x2009;=&#x2009;1.56&#x2009;&#x00B1;&#x2009;0.18<break/>Total cholesterol&#x2009;=&#x2009;5.45&#x2009;&#x00B1;&#x2009;0.20<break/>LDL cholesterol&#x2009;=&#x2009;3.37&#x2009;&#x00B1;&#x2009;0.17<break/>HDL cholesterol&#x2009;=&#x2009;1.37&#x2009;&#x00B1;&#x2009;0.06</td>
</tr>
<tr>
<td align="left" valign="top" rowspan="2">Stendell-Hollis et al. (<xref ref-type="bibr" rid="ref32">32</xref>)</td>
<td align="left" valign="top" rowspan="2">RCT</td>
<td align="left" valign="top" rowspan="2">USA</td>
<td align="left" valign="top">Intervention (<italic>n</italic>)&#x2009;=&#x2009;23<break/>240&#x2009;mL green tea four times daily for 6&#x2009;months</td>
<td align="left" valign="top">Wt&#x2009;=&#x2009;81.9&#x2009;&#x00B1;&#x2009;15.3<break/>BMI&#x2009;=&#x2009;31.0&#x2009;&#x00B1;&#x2009;4.3<break/>Triglycerides&#x2009;=&#x2009;1.8&#x2009;&#x00B1;&#x2009;1.0<break/>Total cholesterol&#x2009;=&#x2009;5.9&#x2009;&#x00B1;&#x2009;1.0<break/>LDL cholesterol&#x2009;=&#x2009;3.8&#x2009;&#x00B1;&#x2009;0.9<break/>HDL cholesterol&#x2009;=&#x2009;1.3&#x2009;&#x00B1;&#x2009;0.39<break/>HOMA-IR&#x2009;=&#x2009;6.9 (7.4)<break/>Glucose&#x2009;=&#x2009;6.5 (1.3)</td>
<td align="left" valign="top">Wt&#x2009;=&#x2009;80.7&#x2009;&#x00B1;&#x2009;14.9<break/>BMI&#x2009;=&#x2009;30.5&#x2009;&#x00B1;&#x2009;4.2<break/>Triglycerides&#x2009;=&#x2009;1.6&#x2009;&#x00B1;&#x2009;2.1<break/>Total cholesterol&#x2009;=&#x2009;5.6&#x2009;&#x00B1;&#x2009;1.0<break/>LDL cholesterol&#x2009;=&#x2009;3.4&#x2009;&#x00B1;&#x2009;1.1<break/>HDL cholesterol&#x2009;=&#x2009;1.4&#x2009;&#x00B1;&#x2009;0.4<break/>HOMA-IR&#x2009;=&#x2009;5.8 (3.4)<break/>Glucose&#x2009;=&#x2009;5.6 (1.0)</td>
<td align="left" valign="top" rowspan="2">After 6&#x2009;months, there were <italic>no significant</italic> changes in weight, BMI, triglycerides, total cholesterol, HDL and LDL cholesterol, glucose and HOMA-IR between the two groups (<italic>p</italic> &#x003E;&#x2009;0.5)</td>
</tr>
<tr>
<td align="left" valign="top">Control (<italic>n</italic>)&#x2009;=&#x2009;16<break/>Placebo tea for 6&#x2009;months</td>
<td align="left" valign="top">Wt&#x2009;=&#x2009;77.8&#x2009;&#x00B1;&#x2009;9.8<break/>BMI&#x2009;=&#x2009;28.7&#x2009;&#x00B1;&#x2009;3.8<break/>Triglycerides&#x2009;=&#x2009;1.7&#x2009;&#x00B1;&#x2009;0.9<break/>Total cholesterol&#x2009;=&#x2009;6.9&#x2009;&#x00B1;&#x2009;1.3<break/>LDL cholesterol&#x2009;=&#x2009;4.7&#x2009;&#x00B1;&#x2009;1.1<break/>HDL cholesterol&#x2009;=&#x2009;1.4&#x2009;&#x00B1;&#x2009;0.4<break/>HOMA-IR&#x2009;=&#x2009;4.1 (1.6)<break/>Glucose&#x2009;=&#x2009;7.0 (1.2)</td>
<td align="left" valign="top">Wt&#x2009;=&#x2009;78.0&#x2009;&#x00B1;&#x2009;9.1<break/>BMI&#x2009;=&#x2009;28.8&#x2009;&#x00B1;&#x2009;3.7<break/>Triglycerides&#x2009;=&#x2009;1.5&#x2009;&#x00B1;&#x2009;0.8<break/>Total cholesterol&#x2009;=&#x2009;6.3&#x2009;&#x00B1;&#x2009;1.6<break/>LDL cholesterol&#x2009;=&#x2009;3.9&#x2009;&#x00B1;&#x2009;1.3<break/>HDL cholesterol&#x2009;=&#x2009;1.6&#x2009;&#x00B1;&#x2009;0.4<break/>HOMA-IR&#x2009;=&#x2009;7.4 (7.4)<break/>Glucose&#x2009;=&#x2009;7.0 (1.0)</td>
</tr>
<tr>
<td align="left" valign="top" rowspan="2">Woerdeman et al.<break/>(<xref ref-type="bibr" rid="ref33">33</xref>)</td>
<td align="left" valign="top" rowspan="2">RCT</td>
<td align="left" valign="top" rowspan="2">Netherlands</td>
<td align="left" valign="top">Intervention (<italic>n</italic>)&#x2009;=&#x2009;14<break/>600&#x2009;mg/day of red wine polyphenols for 8&#x2009;weeks</td>
<td align="left" valign="top">Wt&#x2009;=&#x2009;108&#x2009;&#x00B1;&#x2009;15.2<break/>BMI&#x2009;=&#x2009;33.5<break/>Triglycerides&#x2009;=&#x2009;1.2&#x2009;&#x00B1;&#x2009;1.0<break/>Total cholesterol&#x2009;=&#x2009;4.8&#x2009;&#x00B1;&#x2009;1.2<break/>LDL cholesterol&#x2009;=&#x2009;2.9&#x2009;&#x00B1;&#x2009;1.1<break/>HDL cholesterol&#x2009;=&#x2009;1.2&#x2009;&#x00B1;&#x2009;0.4<break/>HOMA-IR&#x2009;=&#x2009;3.2 (2.0; 4.5)<break/>Glucose&#x2009;=&#x2009;5.3&#x2009;&#x00B1;&#x2009;0.5</td>
<td align="left" valign="top">Wt&#x2009;=&#x2009;109.0&#x2009;&#x00B1;&#x2009;15.8<break/>BMI&#x2009;=&#x2009;&#x2212;<break/>Triglycerides&#x2009;=&#x2009;1.4&#x2009;&#x00B1;&#x2009;1.1<break/>Total cholesterol&#x2009;=&#x2009;4.8&#x2009;&#x00B1;&#x2009;1.1<break/>LDL cholesterol&#x2009;=&#x2009;3.0&#x2009;&#x00B1;&#x2009;1.1<break/>HDL cholesterol&#x2009;=&#x2009;1.2&#x2009;&#x00B1;&#x2009;0.4<break/>HOMA-IR&#x2009;=&#x2009;2.9 (2.1; 3.8)<break/>Glucose =5.3&#x2009;&#x00B1;&#x2009;0.7</td>
<td align="left" valign="top" rowspan="2">There were no significant changes in either total, LDL or HDL cholesterol or triglyceride levels, glucose, or HOMA-IR after red wine supplementation between group</td>
<td/>
<td/>
<td/>
</tr>
<tr>
<td align="left" valign="top">Control (<italic>n</italic>)&#x2009;=&#x2009;15<break/>Placebo for 8&#x2009;weeks</td>
<td align="left" valign="top">Wt&#x2009;=&#x2009;106.4&#x2009;&#x00B1;&#x2009;16.1<break/>BMI&#x2009;=&#x2009;33.1<break/>Triglycerides&#x2009;=&#x2009;1.1&#x2009;&#x00B1;&#x2009;0.7<break/>Total cholesterol&#x2009;=&#x2009;4.5&#x2009;&#x00B1;&#x2009;1.1<break/>LDL cholesterol&#x2009;=&#x2009;2.8&#x2009;&#x00B1;&#x2009;1.0<break/>HDL cholesterol&#x2009;=&#x2009;1.2&#x2009;&#x00B1;&#x2009;0.3<break/>HOMA-IR&#x2009;=&#x2009;2.3 (1.4; 2.7)<break/>Glucose&#x2009;=&#x2009;5.0&#x2009;&#x00B1;&#x2009;0.7</td>
<td align="left" valign="top">Wt&#x2009;=&#x2009;106.6&#x2009;&#x00B1;&#x2009;16.8<break/>BMI&#x2009;=&#x2009;&#x2013;<break/>Triglycerides&#x2009;=&#x2009;1.0&#x2009;&#x00B1;&#x2009;0.8<break/>Total cholesterol&#x2009;=&#x2009;4.4&#x2009;&#x00B1;&#x2009;1.0<break/>LDL cholesterol&#x2009;=&#x2009;2.7&#x2009;&#x00B1;&#x2009;1.0<break/>HDL cholesterol&#x2009;=&#x2009;1.3&#x2009;&#x00B1;&#x2009;0.3<break/>HOMA-IR&#x2009;=&#x2009;2.2 (1.5; 2.8)<break/>Glucose&#x2009;=&#x2009;5.2&#x2009;&#x00B1;&#x2009;0.5</td>
<td/>
</tr>
</tbody>
</table>
<table-wrap-foot>
<p>Values are presented as mean&#x2009;&#x00B1;&#x2009;standard deviation. Wt&#x2009;=&#x2009;weight; BMI&#x2009;=&#x2009;body mass index; HOMA-IR, homeostasis model assessment-insulin resistance; HDL, high-density lipoprotein; LDL, low-density lipoprotein; (&#x2212;) not available.</p>
</table-wrap-foot>
</table-wrap>
<table-wrap position="float" id="tab5">
<label>Table 5</label>
<caption>
<p>Type 2 diabetes mellitus and polyphenol.</p>
</caption>
<table frame="hsides" rules="groups">
<thead>
<tr>
<th align="center" valign="top" colspan="7">Type 2 diabetes mellitus and polyphenol</th>
</tr>
<tr>
<th align="left" valign="top">Author, years</th>
<th align="left" valign="top">Study design</th>
<th align="left" valign="top">Location</th>
<th align="left" valign="top">Intervention vs. control</th>
<th align="left" valign="top">Baseline characteristics of the participants</th>
<th align="left" valign="top">Posttreatment characteristics of the participants</th>
<th align="left" valign="top">Results<break/><italic>p</italic>-value</th>
</tr>
</thead>
<tbody>
<tr>
<td align="left" valign="top" rowspan="2">Aghasi et al. (<xref ref-type="bibr" rid="ref34">34</xref>)</td>
<td align="left" valign="top" rowspan="2">RCT</td>
<td align="left" valign="top" rowspan="2">Iran</td>
<td align="left" valign="top">Intervention (<italic>n</italic> =&#x2009;41)<break/>3&#x2009;g of green cardamom supplement for 10&#x2009;weeks</td>
<td align="left" valign="top">BMI&#x2009;=&#x2009;29.06&#x2009;&#x00B1;&#x2009;3.21<break/>HbA1c (%)&#x2009;=&#x2009;8.19 (0.68)<break/>HOMA-IR&#x2009;=&#x2009;5.01 (1.90)<break/>Triglycerides&#x2009;=&#x2009;158.4 (1.62)<break/>Total cholesterol&#x2009;=&#x2009;155.7 (33.2)<break/>LDL cholesterol&#x2009;=&#x2009;80.2 (20.3)<break/>HDL cholesterol&#x2009;=&#x2009;41.6 (1.2)<break/>Glucose&#x2009;=&#x2009;159.5 (38.7)</td>
<td align="left" valign="top">BMI&#x2009;=&#x2009;28.8&#x2009;&#x00B1;&#x2009;3.1<break/>HbA1c (%)&#x2009;=&#x2009;7.71 (0.67)<break/>HOMA-IR&#x2009;=&#x2009;3.80 (1.65)<break/>Triglycerides&#x2009;=&#x2009;125.8 (1.5)<break/>Total cholesterol&#x2009;=&#x2009;153.43 (34.7)<break/>LDL cholesterol&#x2009;=&#x2009;77.9 (20.4)<break/>HDL cholesterol&#x2009;=&#x2009;41.6 (1.2)<break/>Glucose&#x2009;=&#x2009;146.8 (27.07)</td>
<td align="left" valign="top" rowspan="2">After 10&#x2009;weeks,<break/>There were no significant changes in serum glucose TC, HDL-c and LDL-c levels between the two groups. A significant decrease in serum HbA1C (&#x2212;0.4%), HOMA-IR (&#x2212;1.7) and TG (&#x2212;39.9&#x2009;mg dL&#x2009;&#x2212;&#x2009;1) was observed in the cardamom group</td>
</tr>
<tr>
<td align="left" valign="top">Control group (<italic>n</italic> =&#x2009;42).<break/>Placebo</td>
<td align="left" valign="top">BMI&#x2009;=&#x2009;28.66&#x2009;&#x00B1;&#x2009;4.34<break/>HbA1c (%)&#x2009;=&#x2009;7.27&#x2009;&#x00B1;&#x2009;0.60<break/>HOMA-IR&#x2009;=&#x2009;1.50&#x2009;&#x00B1;&#x2009;0.51<break/>Triglycerides&#x2009;=&#x2009;135.54&#x2009;&#x00B1;&#x2009;51.55<break/>Total cholesterol&#x2009;=&#x2009;142.48&#x2009;&#x00B1;&#x2009;33.55<break/>LDL cholesterol&#x2009;=&#x2009;70.53&#x2009;&#x00B1;&#x2009;26.19<break/>HDL cholesterol&#x2009;=&#x2009;44.83&#x2009;&#x00B1;&#x2009;10.87<break/>Glucose&#x2009;=&#x2009;143.09&#x2009;&#x00B1;&#x2009;37.39</td>
<td align="left" valign="top">BMI&#x2009;=&#x2009;29.2&#x2009;&#x00B1;&#x2009;3.5<break/>HbA1c (%)&#x2009;=&#x2009;7.72 (0.58)<break/>HOMA-IR&#x2009;=&#x2009;4.46 (1.65)<break/>Triglycerides&#x2009;=&#x2009;138.03 (1.44)<break/>Total cholesterol&#x2009;=&#x2009;160.5 (30.27)<break/>LDL cholesterol&#x2009;=&#x2009;87.4 (22.8)<break/>HDL cholesterol&#x2009;=&#x2009;41.6 (1.23)<break/>Glucose&#x2009;=&#x2009;145.8 (23.2)</td>
</tr>
<tr>
<td align="left" valign="top" rowspan="2">Asadi et al. (<xref ref-type="bibr" rid="ref35">35</xref>)</td>
<td align="left" valign="top" rowspan="2">RCT</td>
<td align="left" valign="top" rowspan="2">Iran</td>
<td align="left" valign="top">Melissa. officinalis capsules (700&#x2009;mg/d; <italic>n</italic> =&#x2009;31) twice</td>
<td align="left" valign="top">BMI&#x2009;=&#x2009;28.66&#x2009;&#x00B1;&#x2009;4.34<break/>HbA1c (%)&#x2009;=&#x2009;7.27&#x2009;&#x00B1;&#x2009;0.60<break/>HOMA-IR&#x2009;=&#x2009;1.50&#x2009;&#x00B1;&#x2009;0.51<break/>Triglycerides&#x2009;=&#x2009;135.54&#x2009;&#x00B1;&#x2009;51.55<break/>Total cholesterol&#x2009;=&#x2009;142.48&#x2009;&#x00B1;&#x2009;33.55<break/>LDL cholesterol&#x2009;=&#x2009;70.53&#x2009;&#x00B1;&#x2009;26.19<break/>HDL cholesterol&#x2009;=&#x2009;44.83&#x2009;&#x00B1;&#x2009;10.87<break/>Glucose&#x2009;=&#x2009;143.09&#x2009;&#x00B1;&#x2009;37.39</td>
<td align="left" valign="top">BMI&#x2009;=&#x2009;&#x2212;<break/>HbA1c (%)&#x2009;=&#x2009;6.99&#x2009;&#x00B1;&#x2009;0.68<break/>HOMA-IR&#x2009;=&#x2009;1.30&#x2009;&#x00B1;&#x2009;0.52<break/>Triglycerides&#x2009;=&#x2009;122.03&#x2009;&#x00B1;&#x2009;42.74<break/>Total cholesterol&#x2009;=&#x2009;145.38&#x2009;&#x00B1;&#x2009;31.15<break/>LDL cholesterol&#x2009;=&#x2009;72.46&#x2009;&#x00B1;&#x2009;28.85<break/>HDL cholesterol&#x2009;=&#x2009;48.51&#x2009;&#x00B1;&#x2009;10.55<break/>Glucose&#x2009;=&#x2009;143.29&#x2009;&#x00B1;&#x2009;33.59</td>
<td align="left" valign="top" rowspan="2">After 12&#x2009;weeks, there were significant differences in HbA1c (<italic>p</italic> =&#x2009;0.002), TG<break/>(<italic>p</italic> =&#x2009;0.04), HDL-c (<italic>p</italic> =&#x2009;0.05) between the two group</td>
</tr>
<tr>
<td align="left" valign="top">Control group (<italic>n</italic> =&#x2009;31).<break/>Placebo</td>
<td align="left" valign="top">BMI&#x2009;=&#x2009;28.37&#x2009;&#x00B1;&#x2009;3.71<break/>HbA1c (%)&#x2009;=&#x2009;7.36&#x2009;&#x00B1;&#x2009;0.49<break/>HOMA-IR&#x2009;=&#x2009;1.56&#x2009;&#x00B1;&#x2009;0.62<break/>Triglycerides&#x2009;=&#x2009;143.19&#x2009;&#x00B1;&#x2009;62.19<break/>Total cholesterol&#x2009;=&#x2009;147.09&#x2009;&#x00B1;&#x2009;31.85<break/>LDL cholesterol&#x2009;=&#x2009;70.53&#x2009;&#x00B1;&#x2009;26.19<break/>HDL cholesterol&#x2009;=&#x2009;44.64&#x2009;&#x00B1;&#x2009;9.23<break/>Glucose&#x2009;=&#x2009;138.87&#x2009;&#x00B1;&#x2009;34.59</td>
<td align="left" valign="top">BMI&#x2009;=&#x2009;&#x2212;<break/>HbA1c (%)&#x2009;=&#x2009;7.47&#x2009;&#x00B1;&#x2009;0.74<break/>HOMA-IR&#x2009;=&#x2009;1.42&#x2009;&#x00B1;&#x2009;0.67<break/>Triglycerides&#x2009;=&#x2009;138.67&#x2009;&#x00B1;&#x2009;38.52<break/>Total cholesterol&#x2009;=&#x2009;153.09&#x2009;&#x00B1;&#x2009;26.97<break/>LDL cholesterol&#x2009;=&#x2009;70.53&#x2009;&#x00B1;&#x2009;26.19<break/>HDL cholesterol&#x2009;=&#x2009;44.61&#x2009;&#x00B1;&#x2009;9.29<break/>Glucose&#x2009;=&#x2009;151.80&#x2009;&#x00B1;&#x2009;35.34</td>
</tr>
</tbody>
</table>
<table-wrap-foot>
<p>Values are presented as mean&#x2009;&#x00B1;&#x2009;standard deviation. Wt&#x2009;=&#x2009;weight; BMI&#x2009;=&#x2009;body mass index; HOMA-IR, homeostasis model assessment-insulin resistance; HDL, high-density lipoprotein; LDL, low-density lipoprotein; (&#x2212;) not available.</p>
</table-wrap-foot>
</table-wrap>
</sec>
<sec id="sec22">
<title>Primary outcomes</title>
<sec id="sec23">
<title>Polyphenols and lipid profile</title>
<p>Six studies evaluated the lipid profile, five of which found no significant difference in triglycerides, total cholesterol, LDL cholesterol and HDL cholesterol between the control and the intervention groups (<xref ref-type="bibr" rid="ref30 ref31 ref32 ref33 ref34">30&#x2013;34</xref>). However, Asadi et al. (<xref ref-type="bibr" rid="ref35">35</xref>) showed significant differences in TG (<italic>p</italic> =&#x2009;0.04) and HDL-c (<italic>p</italic> =&#x2009;0.05) between the two groups at the end of the study.</p>
</sec>
</sec>
<sec id="sec24">
<title>Secondary outcomes</title>
<sec id="sec25">
<title>Polyphenols and glucose level</title>
<p>There were no significant changes in glucose levels between the groups (<xref ref-type="bibr" rid="ref30 ref31 ref32 ref33 ref34 ref35">30&#x2013;35</xref>).</p>
</sec>
<sec id="sec26">
<title>Polyphenols and A1c</title>
<p>Only two studies assessed cumulative glucose and found significant differences between groups (<xref ref-type="bibr" rid="ref34">34</xref>, <xref ref-type="bibr" rid="ref35">35</xref>).</p>
</sec>
<sec id="sec27">
<title>Polyphenols and HOMA-IR</title>
<p>Five studies evaluated HOMA-IR, four of which found no difference between the two groups (<xref ref-type="bibr" rid="ref30">30</xref>, <xref ref-type="bibr" rid="ref32">32</xref>, <xref ref-type="bibr" rid="ref33">33</xref>, <xref ref-type="bibr" rid="ref35">35</xref>) while Aghasi et al. (<xref ref-type="bibr" rid="ref34">34</xref>) showed that there is a significant decrease in HOMA-IR (&#x2212;1.7) in the intervention group compared to the control group.</p>
</sec>
<sec id="sec28">
<title>Polyphenols and BMI</title>
<p>Three studies assessed BMI and found no difference between the two groups (<xref ref-type="bibr" rid="ref30">30</xref>, <xref ref-type="bibr" rid="ref32">32</xref>, <xref ref-type="bibr" rid="ref34">34</xref>).</p>
</sec>
<sec id="sec29">
<title>Polyphenols and weight</title>
<p>Three studies measured weight and showed that there is no difference between the two groups (<xref ref-type="bibr" rid="ref30">30</xref>, <xref ref-type="bibr" rid="ref32">32</xref>, <xref ref-type="bibr" rid="ref33">33</xref>).</p>
</sec>
</sec>
</sec>
<sec sec-type="discussion" id="sec30">
<title>Discussion</title>
<p>This systematic review compared the effects of different sources of polyphenols in overweight and obese people with or without type 2 diabetes. The primary outcome was lipid profile and the secondary outcomes were blood glucose, HbA1c (%), HOMA-IR, weight, and body mass index. However, the effects of different sources of polyphenols for obese or overweight adults with or without type 2 diabetes remain unclear.</p>
<sec id="sec31">
<title>Epicatechin</title>
<p>Epicatechin is a polyphenol found in various plant-based foods and beverages such as cocoa, grapes, apples, berries, hazelnuts, walnuts, and tea. Kirch et al. (<xref ref-type="bibr" rid="ref30">30</xref>) investigated whether regular consumption of 25&#x2009;mg of pure epicatechin can affect glucose, HOMA-IR, LDL, HDL, total cholesterol, and triglycerides in overweight or obese people, showing that 2&#x2009;weeks of epicatechin supplementation did not reduce cardiometabolic risk factors with no significant changes in glucose metabolism (glucose, HOMA-IR). Similarly, both Dower et al. (<xref ref-type="bibr" rid="ref15">15</xref>) and Guti&#x00E9;rrez-Salme&#x00E1;n et al. (<xref ref-type="bibr" rid="ref36">36</xref>) showed that regular intake of pure epicatechin (25&#x2013;100&#x2009;mg/day) was not effective or less effective on cardiovascular disease risk factors than comparative cocoa intake. Meta-analyses of randomized controlled trials found positive effects of cocoa consumption on glucose and lipid metabolism (<xref ref-type="bibr" rid="ref14">14</xref>, <xref ref-type="bibr" rid="ref37">37</xref>) that could be predicted by epicatechin intake from cocoa (<xref ref-type="bibr" rid="ref38">38</xref>). However, the results are inconsistent due to different dosing duration and may be due to adherence.</p>
</sec>
<sec id="sec32">
<title>Strawberry and cranberry</title>
<p>There are several different types of phenolic compounds in strawberries and cranberries including phenolic acids, flavonoids, and polymerized molecules (<xref ref-type="bibr" rid="ref39">39</xref>). Several vitro and animal studies have suggested that polyphenols may enhance peripheral glucose absorption in insulin-sensitive areas by enhancing GLUT4 translocation and activity and lowering oxidative stress and inflammation (<xref ref-type="bibr" rid="ref40">40</xref>, <xref ref-type="bibr" rid="ref41">41</xref>). For example, Paquette et al. (<xref ref-type="bibr" rid="ref31">31</xref>) evaluated the effectiveness of berries and strawberries on insulin sensitivity and lipid profile in overweight, obese, and non-diabetic subjects showing that a six-week intervention with 333&#x2009;mg of polyphenols from strawberries and cranberries improved insulin sensitivity but was ineffective in improving cardiac risk factors. However, other studies have shown that eating freeze-dried strawberry powder or cranberry extract has a positive influence on lowering total cholesterol and LDL cholesterol (<xref ref-type="bibr" rid="ref42">42</xref>, <xref ref-type="bibr" rid="ref43">43</xref>). This discrepancy may be due to the delivery of strawberries and cranberries in different forms (juice, dried strawberries, and powder) and the different quantities consumed, which makes it difficult to determine their effect.</p>
</sec>
<sec id="sec33">
<title>Green tea</title>
<p>Epidemiologic and animal research supports the positive effect of regular green tea consumption in decreasing the risk of cardiovascular disease (<xref ref-type="bibr" rid="ref44">44</xref>) and obesity (<xref ref-type="bibr" rid="ref45">45</xref>). There are several hypothesized methods by which green tea and its naturally occurring polyphenolic catechins may modify body weight. For instance, green tea and its derivatives cause glucose malabsorption and downregulate fatty acid synthase (<xref ref-type="bibr" rid="ref46">46</xref>, <xref ref-type="bibr" rid="ref47">47</xref>). Individuals with visceral obesity who consumed 583&#x2009;mg of catechins daily for 12&#x2009;weeks saw significant reductions in body weight and LDL cholesterol compared to the control group (<xref ref-type="bibr" rid="ref48">48</xref>). However, Stendell-Hollis et al. (<xref ref-type="bibr" rid="ref32">32</xref>) evaluated the effect of green tea consumption on weight, body mass index, triglycerides, total cholesterol, HDL and LDL cholesterol, glucose, and HOMA-IR in weight gain showing no significant differences between the participants who consumed 960&#x2009;mL of decaffeinated green tea or placebo daily for 6&#x2009;months.</p>
</sec>
<sec id="sec34">
<title>Red wine</title>
<p>It has been reported that a moderate wine intake might inhibit metabolic syndrome and related medical consequences (<xref ref-type="bibr" rid="ref49">49</xref>). According to preclinical research, red wine polyphenols are beneficial and improve insulin sensitivity in obese animal models. However, the effect of red wine on humans is minimal. Only one randomized control trial was conducted by Woerdeman et al. (<xref ref-type="bibr" rid="ref33">33</xref>) to assess the effection of red wine consumption on total cholesterol, HDL and LDL cholesterol, glucose, and HOMA-IR. The participants were randomized to 600&#x2009;mg/day of red wine polyphenols or placebo daily for 8&#x2009;weeks and there were no significant changes in either total, LDL or HDL cholesterol or triglyceride levels, glucose, and HOMA-IR after red wine supplementation between groups (<italic>p</italic> &#x003E;&#x2009;0.5).</p>
</sec>
<sec id="sec35">
<title>Green cardamom</title>
<p>Green cardamom is a good source of polyphenols with antioxidant properties (<xref ref-type="bibr" rid="ref50">50</xref>). Cardamom supplementation enhanced insulin sensitivity and reduced total cholesterol and LDL-cholesterol in prediabetic women (<xref ref-type="bibr" rid="ref51">51</xref>). However, these outcomes did not differ significantly from the placebo group. According to Azimi et al. (<xref ref-type="bibr" rid="ref52">52</xref>), the lipid profiles of type 2 diabetes people who consumed three glasses of black tea along with 3&#x2009;g of cardamom were improved when compared to the control group which only consumed three glasses of black tea. Furthermore, it has been shown that 3&#x2009;g of cardamom significantly decreased serum HbA1C (&#x2212;0.4%), HOMA-IR (&#x2212;1.7), and TG (&#x2212;39.9&#x2009;mg dL&#x2009;&#x2212;&#x2009;1) in the cardamom group compared to placebo (<xref ref-type="bibr" rid="ref34">34</xref>). However, there were no significant changes in serum glucose TC, HDL-c, and LDL-c levels between the two groups after 10&#x2009;weeks (<xref ref-type="bibr" rid="ref34">34</xref>).</p>
</sec>
<sec id="sec36">
<title><italic>Melissa officinalis</italic> (also known as lemon balm)</title>
<p><italic>Melissa officinalis</italic> is a plant that can lower blood sugar and fat levels due to its abundance of flavonoids (<xref ref-type="bibr" rid="ref53">53</xref>). Studies have shown the lipid-lowering and anti-inflammatory properties of <italic>M. officinalis</italic> (<xref ref-type="bibr" rid="ref53">53</xref>, <xref ref-type="bibr" rid="ref54">54</xref>). Furthermore, Asadi et al. (<xref ref-type="bibr" rid="ref35">35</xref>) assessed the effect of <italic>M. officinalis</italic> intake (700&#x2009;mg/d) versus placebo on HbA1c, triglycerides, total cholesterol, HDL and LDL cholesterol, glucose, and HOMA-IR in individuals with type 2 diabetes, observing significant differences in HbA1c (<italic>p</italic>&#x2009;=&#x2009;0.002), triglycerides (<italic>p</italic>&#x2009;=&#x2009;0.04), and HDL-c (<italic>p</italic>&#x2009;=&#x2009;0.05) between the two groups after 12&#x2009;weeks. <italic>In vitro</italic> and animal experiments also demonstrated that <italic>M. officinalis</italic> reduced blood glucose and lipids (<xref ref-type="bibr" rid="ref55">55</xref>, <xref ref-type="bibr" rid="ref56">56</xref>).</p>
</sec>
<sec id="sec37">
<title>Potential mechanisms</title>
<p>Polyphenols are subject to a series of enzymatic reactions and microbial transformations upon ingestion, culminating in their absorption, distribution, metabolism, and excretion throughout various tissues and organs.</p>
<p>First, the chemical structure of polyphenolic compounds greatly influences their metabolic fate. For example, flavonoids, phenolic acids, and other subclasses exhibit distinct metabolic pathways, leading to the formation of diverse metabolites with different bioactivities (<xref ref-type="bibr" rid="ref57">57</xref>). Phase I and II metabolic reactions, which are mainly facilitated by hepatic enzymes, modify the structure of the polyphenols, making them more water-soluble and leading to their elimination (<xref ref-type="bibr" rid="ref58">58</xref>, <xref ref-type="bibr" rid="ref59">59</xref>).</p>
<p>Moreover, consuming food components together can significantly affect polyphenol metabolism. Interactions with macronutrients, such as lipids and proteins, may affect the absorption kinetics and bioavailability of polyphenols (<xref ref-type="bibr" rid="ref60">60</xref>). In addition, the presence of other bioactive compounds within food matrices can modify polyphenol metabolism, which may enhance or inhibit their bioactivity through synergistic or antagonistic effects (<xref ref-type="bibr" rid="ref61">61</xref>).</p>
<p>Furthermore, individual differences in the composition of the gut microbiota contribute to interindividual differences in polyphenol metabolism. Some microbial species possess the enzymatic machinery necessary for the degradation and biotransformation of polyphenolic compounds, resulting in metabolites that may exhibit distinct physiological effects compared to their parent compounds (<xref ref-type="bibr" rid="ref62">62</xref>).</p>
<p>Understanding the metabolism of polyphenolic compounds is crucial to elucidating their health effects and therapeutic potential. By revealing the complex interplay between nutritional factors, host physiology, and gut microbiota, future research endeavors can pave the way for personalized nutritional interventions aimed at improving the bioavailability of polyphenols and harnessing their beneficial properties for human health and well-being.</p>
</sec>
</sec>
<sec id="sec38">
<title>Strength and limitation</title>
<p>The quality assessment of the included studies was conducted to evaluate the methodological rigor and reliability of the evidence presented. We utilized the NHLBI Quality Assessment for Randomized Control Trials (RCTs) which assesses various aspects of study design, conduct, and reporting.</p>
<p>Overall, the quality of the included polyphenol studies varied. Several studies demonstrated a high level of methodological rigor, including randomized controlled trials (RCTs) with appropriate randomization and blinding procedures. However, certain limitations were observed across the studies. Common issues included small sample sizes, lack of blinding, incomplete outcome data, and potential biases.</p>
<p>Despite these limitations, many studies provided valuable insights into the potential health effects of polyphenols.</p>
<p>It is important to interpret the findings of polyphenol studies with caution, considering the methodological limitations identified. Future research should prioritize high-quality study designs, including well-powered RCTs with long-term follow-up, and systematic reviews with rigorous methodology.</p>
</sec>
<sec sec-type="conclusions" id="sec39">
<title>Conclusion</title>
<p>The current systematic review discussed the effect of different sources of polyphenols in overweight and obese people with or without type 2 diabetes, showing that cardamom significantly decreased serum HbA1C, HOMA-IR, and triglyceride and <italic>M. officinalis</italic> reduced blood sugar fat levels and lipids. However, the data associated with the specific health benefits of polyphenols and their sources in people who are overweight, obese, or have type 2 diabetes are still unclear and further research is required to support their use and prove their benefits.</p>
</sec>
<sec sec-type="data-availability" id="sec40">
<title>Data availability statement</title>
<p>The original contributions presented in the study are included in the article/supplementary material, further inquiries can be directed to the corresponding author.</p>
</sec>
<sec sec-type="author-contributions" id="sec41">
<title>Author contributions</title>
<p>SA: Conceptualization, Data curation, Formal analysis, Funding acquisition, Investigation, Methodology, Project administration, Resources, Software, Supervision, Validation, Visualization, Writing &#x2013; original draft, Writing &#x2013; review &#x0026; editing. MA: Methodology, Writing &#x2013; review &#x0026; editing. BA: Methodology, Writing &#x2013; review &#x0026; editing. AbA: Methodology, Writing &#x2013; review &#x0026; editing. IA: Methodology, Writing &#x2013; review &#x0026; editing. AlA: Methodology, Writing &#x2013; review &#x0026; editing. AmA: Methodology, Writing &#x2013; review &#x0026; editing.</p>
</sec>
</body>
<back>
<sec sec-type="funding-information" id="sec42">
<title>Funding</title>
<p>The author(s) declare that no financial support was received for the research, authorship, and/or publication of this article.</p>
</sec>
<sec sec-type="COI-statement" id="sec43">
<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="sec44">
<title>Publisher&#x2019;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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