{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T04:31:34Z","timestamp":1790224294289,"version":"4.1.0"},"reference-count":40,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2020,10,28]],"date-time":"2020-10-28T00:00:00Z","timestamp":1603843200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Impaired fasting glucose (IFG) is a condition that precedes diabetes and increases the risk of developing it. Studies support the hypoglycemic effect of Cynarascolymus (Cs) extracts due to the content of chlorogenic acid, which is a potent inhibitor of glucose 6-phosphate translocase and of dicaffeoylquinic acid derivatives that modulate the activity of alpha-glucosidase. Given this background, we investigated whether a new highly standardized Cs extract could improve glycemic control, insulin sensitivity and other metabolic parameters (total cholesterol (TC), low-density lipoprotein-cholesterol (LDL-C), high-density lipoprotein-cholesterol (HDL-C) Triglycerides, Apolipo protein B (ApoB), Apolipo protein A (ApoA), waist circumference, visceral adipose tissue (VAT) by dual-energy X-ray absorptiometry (DXA) in overweight subjects with newly diagnosed IFG. Fifty-four subjects (females\/males 26\/28, mean \u00b1 SD age 51.5 \u00b1 6.2) were randomly assigned to the supplemented group (n = 27) and placebo (n = 27). After multiple testing correction, statistically significant interactions between time and group were observed for the primary endpoint glycemia (\u03b2 = 0.36, p &lt; 0.0001) and for the secondary endpoints HDL (\u03b2 = \u22120.10, p &lt; 0.0001), total cholesterol\/HDL (\u03b2 = 0.27, p &lt; 0.0001), LDL (\u03b2 = 0.15, p = 0.005), LDL\/HDL (\u03b2 = 0.23, p = 0.001), insulin (\u03b2 = 1.28, p = 0.04), glycated hemoglobin (\u03b2 = 0.21, p = 0.0002), A1c-derived average glucose (\u03b2 = 0.34, p = 0.0002), ApoB (\u03b2 = 6.00, p = 0.01), ApoA (\u03b2 = \u22124.50, p = 0.04), ApoB\/ApoA (\u03b2 = 0.08, p = 0.003), waist circumference (\u03b2 = 1.89, p = 0.05), VAT\u03b2 = 222.37, p = 0.005). In conclusion, these results confirm that Cs supplementation has a significant effect on metabolic parameters in IFG patients.<\/jats:p>","DOI":"10.3390\/nu12113298","type":"journal-article","created":{"date-parts":[[2020,10,28]],"date-time":"2020-10-28T11:43:06Z","timestamp":1603885386000},"page":"3298","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["The Metabolic Effects of Cynara Supplementation in Overweight and Obese Class I Subjects with Newly Detected Impaired Fasting Glycemia: A Double-Blind, Placebo-Controlled, Randomized Clinical Trial"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8336-4851","authenticated-orcid":false,"given":"Mariangela","family":"Rondanelli","sequence":"first","affiliation":[{"name":"IRCCS Mondino Foundation, 27100 Pavia, Italy"},{"name":"Unit of Human and Clinical Nutrition, Department of Public Health, Experimental and Forensic Medicine, University of Pavia, 27100 Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2819-943X","authenticated-orcid":false,"given":"Antonella","family":"Riva","sequence":"additional","affiliation":[{"name":"Research and Development Unit, Indena, 20139 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6681-7329","authenticated-orcid":false,"given":"Giovanna","family":"Petrangolini","sequence":"additional","affiliation":[{"name":"Research and Development Unit, Indena, 20139 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pietro","family":"Allegrini","sequence":"additional","affiliation":[{"name":"Research and Development Unit, Indena, 20139 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luisa","family":"Bernardinelli","sequence":"additional","affiliation":[{"name":"Department of Brain and Behavioral Science, University of Pavia, 27100 Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9577-8450","authenticated-orcid":false,"given":"Teresa","family":"Fazia","sequence":"additional","affiliation":[{"name":"Department of Brain and Behavioral Science, University of Pavia, 27100 Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1632-1787","authenticated-orcid":false,"given":"Gabriella","family":"Peroni","sequence":"additional","affiliation":[{"name":"Endocrinology and Nutrition Unit, Azienda di Servizi alla Persona \u201cIstituto Santa Margherita\u201d, University of Pavia, 27100 Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1088-6648","authenticated-orcid":false,"given":"Clara","family":"Gasparri","sequence":"additional","affiliation":[{"name":"Endocrinology and Nutrition Unit, Azienda di Servizi alla Persona \u201cIstituto Santa Margherita\u201d, University of Pavia, 27100 Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mara","family":"Nichetti","sequence":"additional","affiliation":[{"name":"Endocrinology and Nutrition Unit, Azienda di Servizi alla Persona \u201cIstituto Santa Margherita\u201d, University of Pavia, 27100 Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Milena Anna","family":"Faliva","sequence":"additional","affiliation":[{"name":"Endocrinology and Nutrition Unit, Azienda di Servizi alla Persona \u201cIstituto Santa Margherita\u201d, University of Pavia, 27100 Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maurizio","family":"Naso","sequence":"additional","affiliation":[{"name":"Endocrinology and Nutrition Unit, Azienda di Servizi alla Persona \u201cIstituto Santa Margherita\u201d, University of Pavia, 27100 Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2720-1473","authenticated-orcid":false,"given":"Simone","family":"Perna","sequence":"additional","affiliation":[{"name":"Department of Biology, Sakhir Campus, College of Science, University of Bahrain, Sakheer P.O. Box 32038, Bahrain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,10,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"708","DOI":"10.1046\/j.1464-5491.2002.00835.x","article-title":"Impaired glucose tolerance and impaired fasting glycaemia: The current status on definition and intervention","volume":"19","author":"Unwin","year":"2002","journal-title":"Diabet. Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2335","DOI":"10.2337\/diacare.26.8.2335","article-title":"Prevalences of diabetes and impaired glucose regulation in a Danish population: The Inter99 study","volume":"26","year":"2003","journal-title":"Diabetes Care"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1186\/1749-8546-4-11","article-title":"Hypoglycemic herbs and their action mechanisms","volume":"4","author":"Hui","year":"2009","journal-title":"Chin. Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"780","DOI":"10.1002\/mnfr.200700075","article-title":"Medication-induced mitochondrial damage and disease","volume":"52","author":"Neustadt","year":"2008","journal-title":"Mol. Nutr. Food Res."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1006\/abbi.1997.0563","article-title":"Chlorogenic acid analogue S 3483: A potent competitive inhibitor of the hepatic and renal glucose-6-phosphatase systems","volume":"351","author":"Arion","year":"1998","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"349","DOI":"10.2174\/138955706776073484","article-title":"Anti-hyperglycemic Potential of Natural Products","volume":"6","author":"Matsui","year":"2006","journal-title":"Mini-Rev. Med. Chem."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1002\/ptr.3285","article-title":"Evidence of glycemia-lowering effect by a Cynara scolymus L. extract in normal and obese rats","volume":"25","author":"Fantini","year":"2011","journal-title":"Phyther. Res."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"23","DOI":"10.4149\/gpb_2010_01_23","article-title":"Combined treatment of tetrahydrocurcumin and chlorogenic acid exerts potential antihyperglycemic effect on streptozotocin-nicotinamide-induced diabetic rats","volume":"29","author":"Karthikesan","year":"2010","journal-title":"Gen. Physiol. Biophys."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1002\/ptr.4950","article-title":"Metabolic management in overweight subjects with naive impaired fasting glycaemia by means of a highly standardized extract from cynara scolymus: A double-blind, placebo-controlled, randomized clinical trial","volume":"28","author":"Rondanelli","year":"2014","journal-title":"Phyther. Res."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Kuczmannov\u00e1, A., Bala\u017eov\u00e1, A., Ra\u010dansk\u00e1, E., Kamen\u00edkov\u00e1, M., Fialov\u00e1, S., Majern\u00edk, J., Nagy, M., G\u00e1l, P., Mu\u010daji, P., and Atanasov, A.G. (2016). Agrimonia eupatoria L. and Cynara cardunculus L. Water Infusions: Comparison of Anti-Diabetic Activities. Molecules, 21.","DOI":"10.3390\/molecules21050564"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"812","DOI":"10.1016\/j.clnu.2015.06.010","article-title":"Impact of diet and nutraceutical supplementation on inflammation in elderly people. Results from the RISTOMED study, an open-label randomized control trial","volume":"35","author":"Ostan","year":"2016","journal-title":"Clin. Nutr."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"838","DOI":"10.1016\/j.foodchem.2017.11.099","article-title":"Potential bioaccessibility and functionality of polyphenols and cynaropicrin from breads enriched with artichoke stem","volume":"245","author":"Colantuono","year":"2018","journal-title":"Food Chem."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Mare, R., Mazza, E., Ferro, Y., Gliozzi, M., Nucera, S., Paone, S., Aversa, I., Pujia, R., Marafioti, G., and Musolino, V. (2020). A new breakfast brioche containing bergamot fiber prevents insulin and glucose increase in healthy volunteers: A pilot study. Minerva Endocrinol.","DOI":"10.23736\/S2724-6507.20.03243-5"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"742","DOI":"10.2337\/diacare.25.4.742","article-title":"The prevention or delay of type 2 diabetes: American Diabetes Association and National Institute of Diabetes, Digestive and Kidney Diseases","volume":"25","author":"Sherwin","year":"2002","journal-title":"Diabetes Care"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1473","DOI":"10.2337\/dc08-0545","article-title":"Translating the A1C assay into estimated average glucose values","volume":"31","author":"Nathan","year":"2008","journal-title":"Diabetes Care"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1138","DOI":"10.2337\/diacare.19.10.1138","article-title":"A prospective analysis of the HOMA model. The Mexico City Diabetes Study","volume":"19","author":"Haffner","year":"1996","journal-title":"Diabetes Care"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"808","DOI":"10.1093\/ajcn\/40.4.808","article-title":"New standards of weight and body composition by frame size and height for assessment of nutritional status of adults and the elderly","volume":"40","author":"Frisancho","year":"1984","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"e238","DOI":"10.1038\/nutd.2016.38","article-title":"Validity of visceral adiposity estimates from DXA against MRI in Kuwaiti men and women","volume":"7","author":"Mohammad","year":"2017","journal-title":"Nutr. Diabetes"},{"key":"ref_19","first-page":"111","article-title":"Nlme: Linear and Nonlinear Mixed Effects Models","volume":"3","author":"Pinheiro","year":"2013","journal-title":"R Package Version"},{"key":"ref_20","first-page":"1165","article-title":"The control of the false discovery rate in multiple testing under dependency","volume":"29","author":"Benjamin","year":"2001","journal-title":"Ann. Stat."},{"key":"ref_21","unstructured":"R Core Team (2017). R: A Language and Environment for Statistical Computing, R Foundation for Statistical Computing."},{"key":"ref_22","first-page":"1","article-title":"Linear and Nonlinear Mixed Effects Models","volume":"3","author":"Pinheiro","year":"2007","journal-title":"R Package Version"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"14","DOI":"10.2174\/0929867321666140826115422","article-title":"Polyphenols-Rich Natural Products for Treatment of Diabetes","volume":"22","author":"Dragan","year":"2014","journal-title":"Curr. Med. Chem."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1007\/s11130-015-0503-8","article-title":"Pharmacological Studies of Artichoke Leaf Extract and Their Health Benefits","volume":"70","author":"Affes","year":"2015","journal-title":"Plant Foods Hum. Nutr."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Ben Salem, M., Ben Abdallah Kolsi, R., Dhouibi, R., Ksouda, K., Charfi, S., Yaich, M., Hammami, S., Sahnoun, Z., Zeghal, K.M., and Jamoussi, K. (2017). Protective effects of Cynara scolymus leaves extract on metabolic disorders and oxidative stress in alloxan-diabetic rats. BMC Complement. Altern. Med., 17.","DOI":"10.1186\/s12906-017-1835-8"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1161","DOI":"10.1016\/j.nut.2011.01.008","article-title":"Effects of flavonoids on \u03b1-glucosidase activity: Potential targets for glucose homeostasis","volume":"27","author":"Pereira","year":"2011","journal-title":"Nutrition"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1032","DOI":"10.2174\/138955708785740580","article-title":"Flavonoids: Cellular and Molecular Mechanism of Action in Glucose Homeostasis","volume":"8","author":"Cazarolli","year":"2008","journal-title":"Mini-Rev. Med. Chem."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1111\/j.1753-4887.2012.00470.x","article-title":"Role of coffee in modulation of diabetes risk","volume":"70","author":"Natella","year":"2012","journal-title":"Nutr. Rev."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"202","DOI":"10.3909\/ricm0474","article-title":"Dysglycemia\/prediabetes and cardiovascular risk factors","volume":"10","author":"Abdullah","year":"2009","journal-title":"Rev. Cardiovasc. Med."},{"key":"ref_30","first-page":"60","article-title":"EL Artichoke (Cynara scolymus L.) Leaves and Heads Extracts as Hypoglycemic and Hypocholesterolemic in Rats","volume":"4","author":"Magied","year":"2016","journal-title":"J. Food Nutr. Res."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"790","DOI":"10.1016\/j.clnu.2017.03.017","article-title":"Antioxidant response to artichoke leaf extract supplementation in metabolic syndrome: A double-blind placebo-controlled randomized clinical trial","volume":"37","author":"Rezazadeh","year":"2018","journal-title":"Clin. Nutr."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"7","DOI":"10.3109\/09637486.2012.700920","article-title":"Beneficial effects of artichoke leaf extract supplementation on increasing HDL-cholesterol in subjects with primary mild hypercholesterolaemia: A double-blind, randomized, placebo-controlled trial","volume":"64","author":"Rondanelli","year":"2013","journal-title":"Int. J. Food Sci. Nutr."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"588","DOI":"10.1016\/j.amjcard.2018.11.018","article-title":"Short-Term Effects of Dry Extracts of Artichokeand Berberis in Hypercholesterolemic Patients Without Cardiovascular Disease","volume":"123","author":"Cicero","year":"2019","journal-title":"Am. J. Cardiol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"882","DOI":"10.3109\/09637486.2013.809405","article-title":"A combined natural supplement lowers LDL cholesterol in subjects with moderate untreated hypercholesterolemia: A randomized placebo-controlled trial","volume":"64","author":"Barrat","year":"2013","journal-title":"Int. J. Food Sci. Nutr."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"547","DOI":"10.1007\/s00394-012-0357-x","article-title":"LDL-cholesterol-lowering effect of a dietary supplement with plant extracts in subjects with moderate hypercholesterolemia","volume":"52","author":"Ogier","year":"2013","journal-title":"Eur. J. Nutr."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1161\/01.ATV.10.4.493","article-title":"\u201cPortal\u201d adipose tissue as a generator of risk factors for cardiovascular disease and diabetes","volume":"10","year":"1990","journal-title":"Arteriosclerosis"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1016\/j.ghir.2006.03.004","article-title":"Visceral obesity, impaired glucose tolerance, metabolic syndrome, and growth hormone therapy","volume":"16","author":"Attallah","year":"2006","journal-title":"Growth Horm. IGF Res."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1016\/j.joim.2018.05.006","article-title":"TCF7L2-rs7903146 polymorphism modulates the effect of artichoke leaf extract supplementation on insulin resistance in metabolic syndrome: A randomized, double-blind, placebo-controlled trial","volume":"16","author":"Rezazadeh","year":"2018","journal-title":"J. Integr. Med."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1002\/ptr.5951","article-title":"Effects of artichoke leaf extract supplementation on metabolic parameters in women with metabolic syndrome: Influence of TCF7L2-rs7903146 and FTO-rs9939609 polymorphisms","volume":"32","author":"Rezazadeh","year":"2018","journal-title":"Phyther. Res."},{"key":"ref_40","first-page":"24","article-title":"Challenges in natural health product research: The importance of standardization","volume":"50","author":"Shan","year":"2007","journal-title":"Proc. West. Pharmacol. Soc."}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/12\/11\/3298\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T10:29:48Z","timestamp":1760178588000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/12\/11\/3298"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,10,28]]},"references-count":40,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2020,11]]}},"alternative-id":["nu12113298"],"URL":"https:\/\/doi.org\/10.3390\/nu12113298","relation":{},"ISSN":["2072-6643"],"issn-type":[{"value":"2072-6643","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,10,28]]}}}