88eecbcda85b44ade51381ec33e03128 pmc_33287432.pdf 3426d8673cbc040776cb425e4d0e35748dd57334 pmc_33287432.pdf 29dc4e2ce4c2d6c0e02463d8c59c8bbfb853a380c3d7c843b5fcee7bb7ea4941 pmc_33287432.pdf Title: Ellagic Acid as a Tool to Limit the Diabetes Burden: Updated Evidence Subject: Oxidative stress contributes not only to the pathogenesis of type 2 diabetes (T2D) but also to diabetic vascular complications. It follows that antioxidants might contribute to limiting the diabetes burden. In this review we focus on ellagic acid (EA), a compound that can be obtained upon intestinal hydrolysis of dietary ellagitannins, a family of polyphenols naturally found in several fruits and seeds. There is increasing research on cardiometabolic effects of ellagitannins, EA, and urolithins (EA metabolites). We updated research conducted on these compounds and (I) glucose metabolism; (II) inflammation, oxidation, and glycation; and (III) diabetic complications. We included studies testing EA in isolation, extracts or preparations enriched in EA, or EA-rich foods (mostly pomegranate juice). Animal research on the topic, entirely conducted in murine models, mostly reported glucose-lowering, antioxidant, anti-inflammatory, and anti-glycation effects, along with prevention of micro- and macrovascular diabetic complications. Clinical research is incipient and mostly involved non-randomized and low-powered studies, which confirmed the antioxidant and anti-inflammatory properties of EA-rich foods, but without conclusive results on glucose control. Overall, EA-related compounds might be potential agents to limit the diabetes burden, but well-designed human randomized controlled trials are needed to fill the existing gap between experimental and clinical research. Keywords: ellagic acid; type 2 diabetes; glucose metabolism; oxidative stress; inflammation; diabetic complications Author: Antonio J. Amor, Carmen Gómez-Guerrero, Emilio Ortega, Aleix Sala-Vila and Iolanda Lázaro Creator: LaTeX with hyperref package Producer: pdfTeX-1.40.18 CreationDate: Fri Dec 4 11:49:08 2020 CET ModDate: Fri Dec 4 12:03:13 2020 CET Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 26 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 469785 bytes Optimized: no PDF version: 1.7 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- ENXZUH+VnURWPalladioL-Bold Type 1 Custom yes yes no 10 0 LSJVCV+EURM10 Type 1 Builtin yes yes no 15 0 ARIQJE+VnURWPalladioL Type 1 Custom yes yes no 19 0 OWQCSJ+URWPalladioL-Ital Type 1 Custom yes yes no 23 0 FJTQFF+URWPalladioL-Bold Type 1 Custom yes yes no 28 0 BWJHMD+URWPalladioL-Roma Type 1 Custom yes yes no 32 0 IELMKZ+Rpxr Type 1 Builtin yes yes no 36 0 KUDXZB+TimesNewRomanPS-BoldItalicMT Type 1C WinAnsi yes yes no 44 0 MCBCCI+SourceSansRoman-Regular Type 1C Custom yes yes no 66 0 MCBCCM+SourceSansRoman.613wght Type 1C Custom yes yes no 70 0 MCBCCO+SourceSansRoman-Bold Type 1C Custom yes yes no 74 0 LGZKLX+Rpxi Type 1 Builtin yes yes no 87 0 RXVDWK+Pxsy Type 1 Builtin yes yes no 97 0 MFIGJL+Rpxb Type 1 Builtin yes yes no 101 0 RRWVCL+URWPalladioL-BoldItal Type 1 Custom yes yes no 124 0 VSHNAE+Rpcxr Type 1 Builtin yes yes no 171 0 Jhove (Rel. 1.28.0, 2023-05-18) Date: 2024-01-31 02:33:46 CET RepresentationInformation: pmc_33287432.pdf ReportingModule: PDF-hul, Rel. 1.12.4 (2023-03-16) LastModified: 2020-12-28 03:46:48 CET Size: 469785 Format: PDF Version: 1.7 Status: Well-Formed and valid SignatureMatches: PDF-hul MIMEtype: application/pdf PDFMetadata: Objects: 763 FreeObjects: 1 IncrementalUpdates: 0 DocumentCatalog: PageLayout: SinglePage PageMode: UseNone Outlines: Item: Title: Introduction Destination: section.1 Item: Title: Ellagic Acid and Glucose Control Destination: section.2 Children: Item: Title: In Vitro Studies Destination: subsection.2.1 Item: Title: Animal Studies Destination: subsection.2.2 Children: Item: Title: Non-Diabetic Murine Models Destination: subsubsection.2.2.1 Item: Title: Streptozotocin-Induced Diabetic Murine Models Destination: subsubsection.2.2.2 Item: Title: Alloxan-Induced Diabetic Murine Models Destination: subsubsection.2.2.3 Item: Title: Other Diabetic Murine Models Destination: subsubsection.2.2.4 Item: Title: Human Studies Destination: subsection.2.3 Item: Title: Anti-Inflammatory, Antioxidant, and Anti-Glycation Properties of Ellagic Acid Destination: section.3 Children: Item: Title: Ellagic Acid and Inflammation Destination: subsection.3.1 Children: Item: Title: In Vitro Studies Destination: subsubsection.3.1.1 Item: Title: Animal Studies Destination: subsubsection.3.1.2 Item: Title: Human Studies Destination: subsubsection.3.1.3 Item: Title: Ellagic Acid and Oxidative Stress Destination: subsection.3.2 Children: Item: Title: In Vitro Studies Destination: subsubsection.3.2.1 Item: Title: Animal Studies Destination: subsubsection.3.2.2 Item: Title: Human Studies Destination: subsubsection.3.2.3 Item: Title: Ellagic Acid and Glycation Destination: subsection.3.3 Children: Item: Title: In Vitro Studies Destination: subsubsection.3.3.1 Item: Title: Animal Studies Destination: subsubsection.3.3.2 Item: Title: Human Studies Destination: subsubsection.3.3.3 Item: Title: Ellagic Acid and Complications of Diabetes Destination: section.4 Children: Item: Title: Microvascular Complications Destination: subsection.4.1 Children: Item: Title: Diabetic Kidney Disease Destination: subsubsection.4.1.1 Item: Title: Retinopathy Destination: subsubsection.4.1.2 Item: Title: Macrovascular Complications Destination: subsection.4.2 Children: Item: Title: Atherosclerosis Destination: subsubsection.4.2.1 Item: Title: Cardiopathy Destination: subsubsection.4.2.2 Item: Title: Neurologic-Related Complications of Diabetes Destination: subsection.4.3 Item: Title: Conclusions Destination: section.5 Item: Title: References Destination: section.5 Info: Title: Ellagic Acid as a Tool to Limit the Diabetes Burden: Updated Evidence Author: Antonio J. Amor, Carmen Gómez-Guerrero, Emilio Ortega, Aleix Sala-Vila and Iolanda Lázaro Subject: Oxidative stress contributes not only to the pathogenesis of type 2 diabetes (T2D) but also to diabetic vascular complications. It follows that antioxidants might contribute to limiting the diabetes burden. In this review we focus on ellagic acid (EA), a compound that can be obtained upon intestinal hydrolysis of dietary ellagitannins, a family of polyphenols naturally found in several fruits and seeds. There is increasing research on cardiometabolic effects of ellagitannins, EA, and urolithins (EA metabolites). We updated research conducted on these compounds and (I) glucose metabolism; (II) inflammation, oxidation, and glycation; and (III) diabetic complications. We included studies testing EA in isolation, extracts or preparations enriched in EA, or EA-rich foods (mostly pomegranate juice). Animal research on the topic, entirely conducted in murine models, mostly reported glucose-lowering, antioxidant, anti-inflammatory, and anti-glycation effects, along with prevention of micro- and macrovascular diabetic complications. Clinical research is incipient and mostly involved non-randomized and low-powered studies, which confirmed the antioxidant and anti-inflammatory properties of EA-rich foods, but without conclusive results on glucose control. Overall, EA-related compounds might be potential agents to limit the diabetes burden, but well-designed human randomized controlled trials are needed to fill the existing gap between experimental and clinical research. 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