{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T09:56:10Z","timestamp":1791453370581,"version":"4.3.3"},"reference-count":55,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2023,9,10]],"date-time":"2023-09-10T00:00:00Z","timestamp":1694304000000},"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>Cocoa is considered a functional food because it is a natural source of macro- and micronutrients. Thus, cocoa is rich in vitamins, minerals, fiber, fatty acids, methylxanthines and flavonoids. In addition to favoring the metabolism of lipids and carbohydrates, the bioactive components of cocoa can have an antioxidant, anti-inflammatory and antimicrobial effect, providing numerous benefits for health. This literature review presents an overview of the effects of cocoa, fruit of the Theobroma cacao tree, on systemic and oral health. Several studies report that cocoa intake may contribute to the prevention of cardiovascular, neurodegenerative, immunological, inflammatory, metabolic and bone diseases, in addition to reducing the risk of vascular alterations and cognitive dysfunctions. On oral health, in vitro studies have shown that cocoa extract exerted an inhibitory effect on the growth, adherence and metabolism of cariogenic and periodontopathogenic bacteria, also inhibiting acid production, glycosyltransferase enzyme activity and the synthesis of insoluble polysaccharides. Additionally, administration of cocoa extract reduced biofilm accumulation and caries development in animals infected with cariogenic species. Clinical studies also reported that the use of mouthwashes containing cocoa extract reduced Streptococcus mutans counts in saliva and dental biofilm formation. In short, these studies highlight the nutritional value of cocoa, considering its clinical applicability, stability and economic accessibility.<\/jats:p>","DOI":"10.3390\/nu15183927","type":"journal-article","created":{"date-parts":[[2023,9,11]],"date-time":"2023-09-11T09:09:21Z","timestamp":1694423361000},"page":"3927","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Biological Properties and Antimicrobial Potential of Cocoa and Its Effects on Systemic and Oral Health"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9123-3560","authenticated-orcid":false,"given":"Simone Ortiz Moura","family":"Fideles","sequence":"first","affiliation":[{"name":"Department of Biological Sciences, Bauru School of Dentistry (FOB\/USP), University of Sao Paulo, Bauru 17012-901, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0783-3246","authenticated-orcid":false,"given":"Adriana de C\u00e1ssia","family":"Ortiz","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, Bauru School of Dentistry (FOB\/USP), University of Sao Paulo, Bauru 17012-901, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlos Henrique Bertoni","family":"Reis","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, Bauru School of Dentistry (FOB\/USP), University of Sao Paulo, Bauru 17012-901, Brazil"},{"name":"Postgraduate Program in Structural and Functional Interactions in Rehabilitation, Postgraduate Department, University of Marilia (UNIMAR), Mar\u00edlia 17525-902, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9914-1262","authenticated-orcid":false,"given":"Daniela Vieira","family":"Buchaim","sequence":"additional","affiliation":[{"name":"Postgraduate Program in Structural and Functional Interactions in Rehabilitation, Postgraduate Department, University of Marilia (UNIMAR), Mar\u00edlia 17525-902, Brazil"},{"name":"Medical School, University Center of Adamantina (UNIFAI), Adamantina 17800-000, Brazil"},{"name":"Graduate Program in Anatomy of Domestic and Wild Animals, Faculty of Veterinary Medicine and Animal Science, University of S\u00e3o Paulo (FMVZ\/USP), S\u00e3o Paulo 05508-270, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5881-2218","authenticated-orcid":false,"given":"Rog\u00e9rio Leone","family":"Buchaim","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, Bauru School of Dentistry (FOB\/USP), University of Sao Paulo, Bauru 17012-901, Brazil"},{"name":"Graduate Program in Anatomy of Domestic and Wild Animals, Faculty of Veterinary Medicine and Animal Science, University of S\u00e3o Paulo (FMVZ\/USP), S\u00e3o Paulo 05508-270, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,9,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1146\/annurev-nutr-071811-150642","article-title":"Cocoa and human health","volume":"33","author":"Ellam","year":"2013","journal-title":"Annu. Rev. Nutr."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2779","DOI":"10.1089\/ars.2010.3697","article-title":"Cocoa and Chocolate in Human Health and Disease","volume":"15","author":"Katz","year":"2011","journal-title":"Antioxid. Redox Signal."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"112121","DOI":"10.1016\/j.fct.2021.112121","article-title":"Impact of cocoa flavanols on human health","volume":"151","author":"Martin","year":"2021","journal-title":"Rev. Food Chem. Toxicol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"620","DOI":"10.1080\/10408398.2012.669428","article-title":"Cocoa agronomy, quality, nutritional, and health aspects","volume":"55","author":"Badrie","year":"2015","journal-title":"Crit. Rev. Food Sci. Nutr."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Li, X., Chen, B., Xie, H., He, Y., Zhong, D., and Chen, D. (2018). Antioxidant Structure-Activity Relationship Analysis of Five Dihydrochalcones. Molecules, 23.","DOI":"10.3390\/molecules23051162"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"10","DOI":"10.3945\/ajcn.116.136051","article-title":"The role of metabolism (and the microbiome) in defining the clinical efficacy of dietary flavonoids","volume":"105","author":"Cassidy","year":"2017","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"576","DOI":"10.3945\/an.113.004465","article-title":"Flavonoids","volume":"4","author":"Birt","year":"2013","journal-title":"Adv. Nutr."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Balenti\u0107, J.P., A\u010dkar, D., Joki\u0107, S., Jozinovi\u0107, A., Babi\u0107, J., Mili\u010devi\u0107, B., \u0160ubari\u0107, D., and Pavlovi\u0107, N. (2018). Cocoa Shell: A By-Product with Great Potential for Wide Application. Molecules, 23.","DOI":"10.3390\/molecules23061404"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1016\/j.fitote.2009.04.006","article-title":"Anti-cariogenic effects of polyphenols from plant stimulant beverages (cocoa, coffee, tea)","volume":"80","author":"Ferrazzano","year":"2009","journal-title":"Fitoterapia"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"859","DOI":"10.1021\/jf072826r","article-title":"Neuroprotective effects of the citrus flavanones against H2O2-induced cytotoxicity in PC12 cells","volume":"56","author":"Hwang","year":"2008","journal-title":"J. Agric. Food Chem."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"220","DOI":"10.4103\/1673-5374.200805","article-title":"Pretreated quercetin protects gerbil hippocampal CA1 pyramidal neurons from transient cerebral ischemic injury by increasing the expression of antioxidant enzymes","volume":"12","author":"Chen","year":"2017","journal-title":"Neural Regen. Res."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Dias, M.C., Pinto, D., and Silva, A.M.S. (2021). Plant Flavonoids: Chemical Characteristics and Biological Activity. Molecules, 26.","DOI":"10.3390\/molecules26175377"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"689044","DOI":"10.3389\/fimmu.2021.689044","article-title":"Potential Implications of Quercetin in Autoimmune Diseases","volume":"12","author":"Shen","year":"2021","journal-title":"Front. Immunol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"e14264","DOI":"10.1111\/jfbc.14264","article-title":"Health benefits of polyphenols: A concise review","volume":"46","author":"Rana","year":"2022","journal-title":"J. Food Biochem."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"901","DOI":"10.1055\/s-0043-104775","article-title":"Correlating In Vitro Target-Oriented Screening and Docking: Inhibition of Matrix Metalloproteinases Activities by Flavonoids","volume":"83","author":"Basile","year":"2017","journal-title":"Planta Med."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1271\/bbb.70.178","article-title":"Flavonoid Composition of Fruit Tissues of Citrus Species","volume":"70","author":"Nogata","year":"2006","journal-title":"Biosci. Biotechnol. Biochem."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"299","DOI":"10.2147\/DDDT.S19931","article-title":"Flavonoids targeting of IkappaB phosphorylation abrogates carcinogen-induced MMP-9 and COX-2 expression in human brain endothelial cells","volume":"5","author":"Annabi","year":"2011","journal-title":"Drug Des. Dev. Ther."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1080\/03008207.2018.1489381","article-title":"Peripheral nerve injury, scarring, and recovery","volume":"60","author":"Wang","year":"2019","journal-title":"Connect. Tissue Res."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"111729","DOI":"10.1016\/j.biopha.2021.111729","article-title":"Mechanistic insights and perspectives involved in neuroprotective action of quercetin","volume":"140","author":"Grewal","year":"2021","journal-title":"Biomed. Pharm."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1080\/01616412.2016.1251711","article-title":"Oxidative stress and mitochondrial dysfunction-linked neurodegenerative disorders","volume":"39","author":"Islam","year":"2017","journal-title":"Neurol. Res."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"and Maurya, P.K. (2022). Health Benefits of Quercetin in Age-Related Diseases. Molecules, 27.","DOI":"10.3390\/molecules27082498"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"964","DOI":"10.2174\/1871527315666160813175406","article-title":"Neuroprotective Effects of Quercetin: From Chemistry to Medicine","volume":"15","author":"Barreca","year":"2016","journal-title":"CNS Neurol. Disord. Drug Targets"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1007\/s00774-007-0753-0","article-title":"Expression of bone resorption genes in osteoarthritis and in osteoporosis","volume":"25","author":"Logar","year":"2007","journal-title":"J. Bone Miner. Metab."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1007\/s11914-014-0212-5","article-title":"The Effects of Flavonoids on Bone","volume":"12","author":"Welch","year":"2014","journal-title":"Curr. Osteoporos. Rep."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1080\/21551197.2012.698220","article-title":"Flavonoid Intake and Bone Health","volume":"31","author":"Weaver","year":"2012","journal-title":"J. Nutr. Gerontol. Geriatr."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1016\/j.ijbiomac.2017.09.014","article-title":"Effects of flavonoids incorporated biological macromolecules based scaffolds in bone tissue engineering","volume":"110","author":"Sanjay","year":"2018","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"931","DOI":"10.1017\/S0007114508169896","article-title":"Cocoa: Antioxidant and immunomodulator","volume":"101","author":"Castell","year":"2009","journal-title":"Br. J. Nutr."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Sorrenti, V., Ali, S., Mancin, L., Davinelli, S., Paoli, A., and Scapagnini, G. (2020). Cocoa Polyphenols and Gut Microbiota Interplay: Bioavailability, Prebiotic Effect, and Impact on Human Health. Nutrients, 12.","DOI":"10.3390\/nu12071908"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1093\/ajcn\/87.1.175","article-title":"Chocolate consumption and bone density in older women","volume":"87","author":"Hodgson","year":"2008","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1007\/s00223-016-0215-6","article-title":"Theobromine Upregulates Osteogenesis by Human Mesenchymal Stem Cells In Vitro and Accelerates Bone Development in Rats","volume":"100","author":"Clough","year":"2017","journal-title":"Calcif. Tissue Int."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1799","DOI":"10.1902\/jop.2009.090270","article-title":"Preventive effects of a cocoa-enriched diet on gingival oxidative stress in experimental periodontitis","volume":"80","author":"Tomofuji","year":"2009","journal-title":"J. Periodontol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1016\/S0076-6879(99)00123-8","article-title":"8-Hydroxydeoxyguanosine and 8-hydroxyguanine as biomarkers of oxidative DNA damage","volume":"300","author":"Helbock","year":"1999","journal-title":"Methods Enzymol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.mam.2008.08.006","article-title":"Glutathione: Overview of its protective roles, measurement, and biosynthesis","volume":"30","author":"Forman","year":"2009","journal-title":"Mol. Asp. Med."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"632","DOI":"10.1111\/j.1749-6632.1999.tb07747.x","article-title":"The citrus flavonoid nobiletin suppresses the production and gene expression of matrix metalloproteinases-9\/gelatinase B in rabbit synovial cells","volume":"878","author":"Ito","year":"1999","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1016\/j.archoralbio.2017.07.006","article-title":"The effect of active components from citrus fruits on dentin MMPs","volume":"83","author":"Liu","year":"2017","journal-title":"Arch. Oral Biol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1111\/eos.12225","article-title":"Inhibition of dentine collagen degradation by hesperidin: An in situ study","volume":"123","author":"Takatsuka","year":"2015","journal-title":"Eur. J. Oral Sci."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1080\/00016350600963640","article-title":"The role of matrix metalloproteinases in the oral environment","volume":"65","author":"Hannas","year":"2007","journal-title":"Acta Odontol. Scand."},{"key":"ref_38","first-page":"71","article-title":"The effects of host derived metalloproteinases on dentin Bond and the role of MMPs inhibitors on dentin matrix degradation","volume":"7","author":"Longhi","year":"2015","journal-title":"Oral Implant."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1016\/j.jdent.2011.03.002","article-title":"Effect of hesperidin in vitro on root dentine collagen and demineralization","volume":"39","author":"Hiraishi","year":"2011","journal-title":"J. Dent."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"362","DOI":"10.4012\/dmj.2011-203","article-title":"In vitro effect of hesperidin on root dentin collagen and de\/re-mineralization","volume":"31","author":"Islam","year":"2012","journal-title":"Dent. Mater. J."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1749","DOI":"10.1177\/00220345790580071901","article-title":"Effect of water soluble components derived from cocoa on plaque formation","volume":"58","author":"Palenik","year":"1979","journal-title":"J. Dent. Res."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"2000","DOI":"10.1177\/00220345010800111001","article-title":"Identification of cariostatic substances in the cacao bean husk: Their anti-glucosyltransferase and antibacterial activities","volume":"80","author":"Osawa","year":"2001","journal-title":"J. Dent. Res."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1111\/j.1600-0722.2004.00134.x","article-title":"Inhibitory effects of cacao bean husk extract on plaque formation in vitro and in vivo","volume":"112","author":"Matsumoto","year":"2004","journal-title":"Eur. J. Oral Sci."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"639","DOI":"10.1016\/S0003-9969(00)00042-X","article-title":"Caries inhibitory activity of cacao bean husk extract in in-vitro and animal experiments","volume":"45","author":"Ooshima","year":"2000","journal-title":"Arch. Oral Biol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"342","DOI":"10.1159\/000104791","article-title":"The antibacterial activity of plant extracts containing polyphenols against Streptococcus mutans","volume":"41","author":"Smullen","year":"2007","journal-title":"Caries Res."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1111\/j.1600-0722.2006.00386.x","article-title":"The effect of cocoa polyphenols on the growth, metabolism, and biofilm formation by Streptococcus mutans and Streptococcus sanguinis","volume":"114","author":"Percival","year":"2006","journal-title":"Eur. J. Oral Sci."},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Lagha, A.B., Huacho, P.M., and Grenier, D. (2021). A cocoa (Theobroma cacao L.) extract impairs the growth, virulence properties, and inflammatory potential of Fusobacterium nucleatum and improves oral epithelial barrier function. PLoS ONE, 16.","DOI":"10.1371\/journal.pone.0252029"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"76","DOI":"10.4103\/1735-3327.250975","article-title":"Effect of theobromine in antimicrobial activity: An in vitro study","volume":"16","author":"Lakshmi","year":"2019","journal-title":"Dent. Res. J."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1436","DOI":"10.3855\/jidc.14966","article-title":"Antimicrobial effect of natural kinds of toothpaste on oral pathogenic bact\u00e9ria","volume":"15","author":"Demir","year":"2021","journal-title":"J. Infect. Dev. Ctries."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"841","DOI":"10.1055\/a-1499-7829","article-title":"Evaluation of Cocoa Bean Shell Antimicrobial Activity: A Tentative Assay Using a Metabolomic Approach for Active Compound Identification","volume":"87","author":"Ribeiro","year":"2021","journal-title":"Planta Med."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"67","DOI":"10.4103\/0970-4388.41619","article-title":"Chocolate mouth rinse: Effect on plaque accumulation and mutans streptococci counts when used by children","volume":"26","author":"Srikanth","year":"2008","journal-title":"J. Indian Soc. Pedod. Prev. Dent."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"120","DOI":"10.4103\/0970-4388.180414","article-title":"The role of cacao extract in reduction of the number of mutans streptococci colonies in the saliva of 12\u201314 year-old-children","volume":"34","author":"Fajriani","year":"2016","journal-title":"J. Indian Soc. Pedod. Prev. Dent."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1007\/BF03262816","article-title":"Comparative evaluation of chlorhexidine mouthrinse versus cacao bean husk extract mouthrinse as antimicrobial agents in children","volume":"12","author":"Vivek","year":"2011","journal-title":"Eur. Arch. Paediatr. Dent."},{"key":"ref_54","first-page":"e4968","article-title":"Comparative Evaluation of Cocoa Bean Husk, Ginger and Chlorhexidine Mouth Washes in the Reduction of Steptococcus Mutans and Lactobacillus Count in Saliva: A Randomized Controlled Trial","volume":"11","author":"Shrimathi","year":"2019","journal-title":"Cureus"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"54","DOI":"10.5005\/jp-journals-10005-2494","article-title":"Characterization of Cocoa Bean Husk Extract Particles and its Comparison as a Mouthrinse with Different Vehicles in Children aged 7\u201312 Years","volume":"16","author":"Kibriya","year":"2023","journal-title":"Int. J. Clin. 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