{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T15:41:28Z","timestamp":1788968488909,"version":"build-2803163510"},"reference-count":62,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2025,12,10]],"date-time":"2025-12-10T00:00:00Z","timestamp":1765324800000},"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>Background: Rheumatoid arthritis (RA) is a chronic autoimmune disease driven by persistent inflammation and oxidative stress. Ilex paraguariensis (yerba mate) contains bioactive compounds\u2014particularly chlorogenic acids, quercetin, and rutin\u2014with documented antioxidant and anti-inflammatory properties. Objectives: To systematically review the mechanistic and clinical evidence on Ilex paraguariensis and its main constituents in RA-relevant inflammatory, oxidative, and bone metabolic pathways. Methods: Following PRISMA 2020, PubMed\/MEDLINE, LILACS, and SciELO were searched up to September 2025. Eligible studies included yerba mate preparations (last 10 years) or isolated compounds (last 5 years) assessing RA-relevant clinical, inflammatory, oxidative, or bone metabolic outcomes. Non-original studies were excluded. Owing to heterogeneity, findings were narratively synthesized, and risk of bias was evaluated using RoB 2, ROBINS-I, OHAT, and SYRCLE. Results: Twenty-three studies met inclusion criteria: 11 human (clinical or observational), 7 human-based in vitro, and 5 animal studies. Interventions with yerba mate infusions or standardized extracts suggest reductions in inflammatory markers (e.g., C-reactive protein, interleukin-6) and indicate improvements in glutathione-related oxidative balance. Evidence from isolated compounds, particularly quercetin and rutin, suggests comparable anti-inflammatory and antioxidant effects. Preclinical studies appear to indicate modulation of inflammatory and redox pathways relevant to RA. Conclusions: Yerba mate and its constituents show preliminary indications of anti-inflammatory and antioxidant effects with potential relevance to RA pathophysiology. However, in the absence of clinical trials in RA patients, conclusions remain tentative, constrained by small sample sizes, methodological heterogeneity, species differences, and internal validity concerns. Future research should include rigorously designed randomized trials and mechanistic studies using advanced human-relevant platforms, such as organoids and organ-on-chip systems.<\/jats:p>","DOI":"10.3390\/nu17243853","type":"journal-article","created":{"date-parts":[[2025,12,10]],"date-time":"2025-12-10T14:22:40Z","timestamp":1765376560000},"page":"3853","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Yerba Mate (Ilex paraguariensis) and Rheumatoid Arthritis: A Systematic Review of Mechanistic and Clinical Evidence"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3425-9195","authenticated-orcid":false,"given":"Manuela","family":"Cassotta","sequence":"first","affiliation":[{"name":"Research Group on Food, Nutritional Biochemistry and Health, Universidad Europea del Atl\u00e1ntico, Isabel Torres 21, 39011 Santander, Spain"},{"name":"Joint Laboratory on Food Science, Nutrition, and Intelligent Processing of Foods, Polytechnic University of Marche, Italy, Universidad Europea del Atl\u00e1ntico Spain and Jiangsu University, China, at Universidad Europea del Atl\u00e1ntico, 39011 Santander, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-1943-7066","authenticated-orcid":false,"given":"Qingwei","family":"Cao","sequence":"additional","affiliation":[{"name":"Department of Clinical Sciences, Universit\u00e0 Politecnica delle Marche, 60131 Ancona, Italy"},{"name":"Joint Laboratory on Food Science, Nutrition, and Intelligent Processing of Foods, Polytechnic University of Marche, Italy, Universidad Europea del Atl\u00e1ntico Spain and Jiangsu University, China, at the Polytechnic University of Marche, 60130 Ancona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-4018-2685","authenticated-orcid":false,"given":"Haixia","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Clinical Sciences, Universit\u00e0 Politecnica delle Marche, 60131 Ancona, Italy"},{"name":"Joint Laboratory on Food Science, Nutrition, and Intelligent Processing of Foods, Polytechnic University of Marche, Italy, Universidad Europea del Atl\u00e1ntico Spain and Jiangsu University, China, at the Polytechnic University of Marche, 60130 Ancona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7941-2849","authenticated-orcid":false,"given":"Carlos Rabeiro","family":"Martinez","sequence":"additional","affiliation":[{"name":"Department of Clinical Sciences, Universit\u00e0 Politecnica delle Marche, 60131 Ancona, Italy"},{"name":"Joint Laboratory on Food Science, Nutrition, and Intelligent Processing of Foods, Polytechnic University of Marche, Italy, Universidad Europea del Atl\u00e1ntico Spain and Jiangsu University, China, at the Polytechnic University of Marche, 60130 Ancona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0800-8563","authenticated-orcid":false,"given":"Luis Alonso","family":"Dzul Lopez","sequence":"additional","affiliation":[{"name":"Research Group on Food, Nutritional Biochemistry and Health, Universidad Europea del Atl\u00e1ntico, Isabel Torres 21, 39011 Santander, Spain"},{"name":"Faculty of Nutrition and Dietetics, Universidad Internacional Iberoamericana, Campeche 24560, Mexico"},{"name":"Research Group on Food, Nutritional Biochemistry and Health, Universidad de La Romana, La Romana 22000, Dominican Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7065-4793","authenticated-orcid":false,"given":"Santos","family":"Gracia Villar","sequence":"additional","affiliation":[{"name":"Research Group on Food, Nutritional Biochemistry and Health, Universidad Europea del Atl\u00e1ntico, Isabel Torres 21, 39011 Santander, Spain"},{"name":"Faculty of Nutrition and Dietetics, Universidad Internacional Iberoamericana, Campeche 24560, Mexico"},{"name":"Faculty of Human Nutrition and Dietetics, Universidade Internacional do Cuanza, Cuito EN250, Bi\u00e9, Angola"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7250-1782","authenticated-orcid":false,"given":"Maurizio","family":"Battino","sequence":"additional","affiliation":[{"name":"Research Group on Food, Nutritional Biochemistry and Health, Universidad Europea del Atl\u00e1ntico, Isabel Torres 21, 39011 Santander, Spain"},{"name":"Department of Clinical Sciences, Universit\u00e0 Politecnica delle Marche, 60131 Ancona, Italy"},{"name":"Joint Laboratory on Food Science, Nutrition, and Intelligent Processing of Foods, Polytechnic University of Marche, Italy, Universidad Europea del Atl\u00e1ntico Spain and Jiangsu University, China, at the Polytechnic University of Marche, 60130 Ancona, Italy"},{"name":"International Joint Research Laboratory of Intelligent Agriculture and Agri-Products Processing, Jiangsu University, Zhenjiang 212013, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8151-9132","authenticated-orcid":false,"given":"Francesca","family":"Giampieri","sequence":"additional","affiliation":[{"name":"Research Group on Food, Nutritional Biochemistry and Health, Universidad Europea del Atl\u00e1ntico, Isabel Torres 21, 39011 Santander, Spain"},{"name":"Department of Clinical Sciences, Universit\u00e0 Politecnica delle Marche, 60131 Ancona, Italy"},{"name":"Joint Laboratory on Food Science, Nutrition, and Intelligent Processing of Foods, Polytechnic University of Marche, Italy, Universidad Europea del Atl\u00e1ntico Spain and Jiangsu University, China, at the Polytechnic University of Marche, 60130 Ancona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,10]]},"reference":[{"key":"ref_1","unstructured":"Chauhan, K., Jandu, J.S., Brent, L.H., and Al-Dhahir, M.A. (2025). 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