{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T11:38:42Z","timestamp":1790854722253,"version":"4.1.0"},"reference-count":22,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T00:00:00Z","timestamp":1772150400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100005632","name":"National Centre for Research and Development","doi-asserted-by":"publisher","award":["POIR.01.01.01-00-0985\/17"],"award-info":[{"award-number":["POIR.01.01.01-00-0985\/17"]}],"id":[{"id":"10.13039\/501100005632","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Background\/Objectives: Advanced glycation end products (AGEs) and oxidative stress increase with aging and are implicated in Alzheimer\u2019s disease (AD). We developed an anti-glycation blend using LC-MS-based screening and assessed its effects on oxidative and glycation-related biomarkers in humans. Methods: Twelve candidate compounds were screened in a BSA\u2013glucose model using LC-MS peptide mapping to quantify lysine glycation and rank inhibitory activity. The top candidates were combined into a three-compound blend (quercetin, rutin, genistein). In a randomized, double-blind, placebo-controlled 3-month trial, older healthy adults (n = 30) and individuals with AD (n = 30) received anti-AGE blend (n = 15 in older group and n = 15 in AD group) or placebo (n = 15 in older group and n = 15 in AD group). Serum malondialdehyde and urinary N\u03b5-(carboxymethyl)lysine were measured pre\u2013post intervention. Pre\/post and between-arm comparisons within each population were performed using REML ANOVA with Tukey post hoc tests. Serum MDA (malondialdehyde) and urinary CML (N\u03b5-(carboxymethyl)lysine) were prespecified biomarker outcomes and are reported here as co-primary biomarker endpoints. No formal a priori sample size calculation was performed; the study size was feasibility-based. Results: LC-MS screening identified genistein, quercetin, and rutin as the most consistent inhibitors of glucose-driven BSA glycation. In older healthy adults, serum MDA decreased after anti-AGE supplementation (p &lt; 0.001) and differed from the placebo (p &lt; 0.01), while no change was observed within the placebo group (ns). In the AD cohort, MDA did not change significantly from baseline within either arm (ns), but post-intervention MDA was lower in anti-AGE than in the placebo (p &lt; 0.05). Urinary CML was unchanged in older healthy adults (ns in both arms), whereas in AD, it decreased after anti-AGE supplementation (p &lt; 0.01) and differed from the placebo (p &lt; 0.05). Conclusions: A screening-guided anti-glycation blend supplementation was associated with changes in selected biomarkers in humans: MDA decreased across cohorts, while CML decreased selectively in AD. Larger trials with extended biomarker panels and LC\u2013MS\/MS confirmation are warranted.<\/jats:p>","DOI":"10.3390\/nu18050789","type":"journal-article","created":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T17:05:16Z","timestamp":1772211916000},"page":"789","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Effect of a Nutraceutical Combination on Oxidative Stress Biomarkers in Healthy Subjects and Patients with Alzheimer\u2019s Disease"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8124-3626","authenticated-orcid":false,"given":"Rafa\u0142","family":"Jastrz\u0105b","sequence":"first","affiliation":[{"name":"Research and Development Center, Olimp Laboratories Sp. z o.o., 39-200 D\u0119bica, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrzej","family":"Ma\u0142ecki","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Biology, Institute of Physiotherapy and Health Sciences, Academy of Physical Education, 40-065 Katowice, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"El\u017cbieta","family":"Kmiecik-Ma\u0142ecka","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Biology, Institute of Physiotherapy and Health Sciences, Academy of Physical Education, 40-065 Katowice, Poland"},{"name":"Neurorehabilitation Ward, Silesian Voivodship Hospital No 5, 41-200 Sosnowiec, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5081-8343","authenticated-orcid":false,"given":"Agnieszka","family":"Gorzkowska","sequence":"additional","affiliation":[{"name":"Department of Neurology, School of Health Sciences, Medical University of Silesia in Katowice, 40-007 Katowice, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kamil","family":"Kubas","sequence":"additional","affiliation":[{"name":"Research and Development Center, Olimp Laboratories Sp. z o.o., 39-200 D\u0119bica, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Justyna","family":"Wid\u0142ak-Kargul","sequence":"additional","affiliation":[{"name":"Research and Development Center, Olimp Laboratories Sp. z o.o., 39-200 D\u0119bica, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Damian","family":"Wolman","sequence":"additional","affiliation":[{"name":"Research and Development Center, Olimp Laboratories Sp. z o.o., 39-200 D\u0119bica, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katarzyna","family":"Matkiewicz","sequence":"additional","affiliation":[{"name":"Research and Development Center, Olimp Laboratories Sp. z o.o., 39-200 D\u0119bica, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8668-8878","authenticated-orcid":false,"given":"Marta","family":"Nowacka-Chmielewska","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Biology, Institute of Physiotherapy and Health Sciences, Academy of Physical Education, 40-065 Katowice, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela","family":"Li\u015bkiewicz","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Biology, Institute of Physiotherapy and Health Sciences, Academy of Physical Education, 40-065 Katowice, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7377-4603","authenticated-orcid":false,"given":"Konstancja","family":"Grabowska","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Biology, Institute of Physiotherapy and Health Sciences, Academy of Physical Education, 40-065 Katowice, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mateusz","family":"Grabowski","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Biology, Institute of Physiotherapy and Health Sciences, Academy of Physical Education, 40-065 Katowice, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0684-1305","authenticated-orcid":false,"given":"Natalia","family":"Pondel","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Biology, Institute of Physiotherapy and Health Sciences, Academy of Physical Education, 40-065 Katowice, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7866-3689","authenticated-orcid":false,"given":"Gabriela","family":"Pocz\u0105tek","sequence":"additional","affiliation":[{"name":"Department of Neurology, Faculty of Health Sciences in Katowice, Medical University of Silesia, 40-007 Katowice, Poland"},{"name":"Doctoral School of Medical and Health Sciences, Silesian Medical University, 40-007 Katowice, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriela","family":"K\u0142odowska","sequence":"additional","affiliation":[{"name":"Neuro-Care Medical Center, 40-749 Katowice, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1265-973X","authenticated-orcid":false,"given":"Jennifer","family":"Mytych","sequence":"additional","affiliation":[{"name":"Research and Development Center, Olimp Laboratories Sp. z o.o., 39-200 D\u0119bica, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,2,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"763","DOI":"10.1016\/j.neurobiolaging.2009.04.016","article-title":"Advanced Glycation Endproducts and Their Receptor RAGE in Alzheimer\u2019s Disease","volume":"32","author":"Srikanth","year":"2011","journal-title":"Neurobiol. Aging"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1038\/s12276-021-00561-7","article-title":"Advanced Glycation End Products (AGEs) and Other Adducts in Aging-Related Diseases and Alcohol-Mediated Tissue Injury","volume":"53","author":"Rungratanawanich","year":"2021","journal-title":"Exp. Mol. Med."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Boccardi, V., Mancinetti, F., and Mecocci, P. (2025). Oxidative Stress, Advanced Glycation End Products (AGEs), and Neurodegeneration in Alzheimer\u2019s Disease: A Metabolic Perspective. Antioxidants, 14.","DOI":"10.20944\/preprints202507.1256.v1"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1039\/C5FO00918A","article-title":"Carboxymethyl-Lysine: Thirty Years of Investigation in the Field of AGE Formation","volume":"7","year":"2016","journal-title":"Food Funct."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1016\/j.jmsacl.2023.08.001","article-title":"GC-MS and GC-MS\/MS Measurement of Malondialdehyde (MDA) in Clinical Studies: Pre-Analytical and Clinical Considerations","volume":"30","author":"Tsikas","year":"2023","journal-title":"J. Mass Spectrom. Adv. Clin. Lab"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"106668","DOI":"10.1016\/j.fitote.2025.106668","article-title":"Effects and Mechanisms of Dietary Polyphenols in Ameliorating Glycolipid Metabolic Disorders: Inhibition of Advanced Glycation End Products","volume":"184","author":"Wang","year":"2025","journal-title":"Fitoterapia"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"3145","DOI":"10.1007\/s10439-024-03499-9","article-title":"Advanced Glycation End Products and Health: A Systematic Review","volume":"52","author":"Zhu","year":"2024","journal-title":"Ann. Biomed. Eng."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Tsao, J.-P., Bernard, J.R., Hsu, H.-C., Hsu, C.-L., Liao, S.-F., and Cheng, I.-S. (2022). Short-Term Oral Quercetin Supplementation Improves Post-exercise Insulin Sensitivity, Antioxidant Capacity and Enhances Subsequent Cycling Time to Exhaustion in Healthy Adults: A Pilot Study. Front. Nutr., 9.","DOI":"10.3389\/fnut.2022.875319"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"490","DOI":"10.1016\/j.jcjd.2019.04.007","article-title":"Effectiveness of Genistein Supplementation on Metabolic Factors and Antioxidant Status in Postmenopausal Women with Type 2 Diabetes Mellitus","volume":"43","author":"Braxas","year":"2019","journal-title":"Can. J. Diabetes"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"774","DOI":"10.1038\/sj.ejcn.1601090","article-title":"Bioavailability and efficiency of rutin as an antioxidant: A human supplementation study","volume":"54","author":"Boyle","year":"2000","journal-title":"Eur. J. Clin. Nutr."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1426","DOI":"10.3945\/ajcn.115.125427","article-title":"Diet low in advanced glycation end products increases insulin sensitivity in healthy overweight individuals: A double-blind, randomized, crossover trial","volume":"103","author":"Soldatos","year":"2016","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1093\/gerona\/62.4.427","article-title":"Circulating Glycotoxins and Dietary Advanced Glycation Endproducts: Two Links to Inflammatory Response, Oxidative Stress, and Aging","volume":"62","author":"Uribarri","year":"2007","journal-title":"J. Gerontol. Ser. A Biol. Sci. Med. Sci."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/j.ab.2016.10.021","article-title":"Assessment of Lipid Peroxidation by Measuring Malondialdehyde (MDA) and Relatives in Biological Samples: Analytical and Biological Challenges","volume":"524","author":"Tsikas","year":"2017","journal-title":"Anal. Biochem."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"9982","DOI":"10.1074\/jbc.271.17.9982","article-title":"The Advanced Glycation End Product, N\u220a-(carboxymethyl)lysine, Is a Product of Both Lipid Peroxidation and Glycoxidation Reactions","volume":"271","author":"Fu","year":"1996","journal-title":"J. Biol. Chem."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1016\/S0165-0173(96)00016-1","article-title":"Advanced Glycation Endproducts in Ageing and Alzheimer\u2019s Disease","volume":"23","author":"Thome","year":"1997","journal-title":"Brain Res. Rev."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"238485","DOI":"10.1155\/2014\/238485","article-title":"Role of Methylglyoxal in Alzheimer\u2019s Disease","volume":"2014","author":"Angeloni","year":"2014","journal-title":"BioMed Res. Int."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"656","DOI":"10.1016\/j.freeradbiomed.2009.11.019","article-title":"Rutin Metabolites: Novel Inhibitors of Nonoxidative Advanced Glycation End Products","volume":"48","author":"Pashikanti","year":"2010","journal-title":"Free Radic. Biol. Med."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"776","DOI":"10.1093\/jn\/nxz017","article-title":"Dietary Genistein Inhibits Methylglyoxal-Induced Advanced Glycation End Product Formation in Mice Fed a High-Fat Diet","volume":"149","author":"Zhao","year":"2019","journal-title":"J. Nutr."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"882","DOI":"10.1080\/09168451.2017.1282805","article-title":"Quercetin Inhibits Advanced Glycation End Product Formation via Chelating Metal Ions, Trapping Methylglyoxal, and Trapping Reactive Oxygen Species","volume":"81","author":"Bhuiyan","year":"2017","journal-title":"Biosci. Biotechnol. Biochem."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"787","DOI":"10.1007\/s11033-020-06084-0","article-title":"A Review on Mechanism of Inhibition of Advanced Glycation End Products Formation by Plant Derived Polyphenolic Compounds","volume":"48","author":"Anwar","year":"2021","journal-title":"Mol. Biol. Rep."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1016\/j.biochi.2025.12.004","article-title":"A Comprehensive Review on the Advanced Glycation End Products Detection: From Conventional to Advanced Approaches","volume":"242","author":"Sahoo","year":"2025","journal-title":"Biochimie"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"546","DOI":"10.1016\/j.xkme.2021.02.013","article-title":"Urinary Biomarkers and Kidney Outcomes: Impact of Indexing versus Adjusting for Urinary Creatinine","volume":"3","author":"Wettersten","year":"2021","journal-title":"Kidney Med."}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/18\/5\/789\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,4]],"date-time":"2026-03-04T09:03:38Z","timestamp":1772615018000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/18\/5\/789"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2,27]]},"references-count":22,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2026,3]]}},"alternative-id":["nu18050789"],"URL":"https:\/\/doi.org\/10.3390\/nu18050789","relation":{},"ISSN":["2072-6643"],"issn-type":[{"value":"2072-6643","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2,27]]}}}