{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T14:09:20Z","timestamp":1785247760873,"version":"3.55.0"},"reference-count":36,"publisher":"MDPI AG","issue":"12","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\/"}],"funder":[{"DOI":"10.13039\/100006756","name":"Brigham Young University","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100006756","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Life"],"abstract":"<jats:p>Chronic low-grade inflammation is a central contributor to the development of cardiovascular disease, metabolic dysfunction, autoimmune disorders, and cognitive decline. Blood-based biomarkers, such as C-reactive protein (CRP), ferritin, homocysteine, white blood cell (WBC) count, and anti-thyroid peroxidase (anti-TPO) antibodies enable quantification and monitoring of systemic inflammation over time. We aimed to evaluate the impact of a 12-week personalized, biomarker-guided supplementation program including micronutrients, hormone support, and peptides on inflammatory and immune-related biomarkers across age- and sex-stratified adult cohorts. Participants (n = 48; 8 per group) were stratified by sex and age (40\u201349, 50\u201359, 60\u201369 years) and underwent blood testing at baseline and 12 weeks. Personalized protocols were developed based on individual biomarker profiles and included targeted interventions with vitamin D, omega-3 fatty acids, B vitamins, zinc, selenium, hormone optimization, and other supportive agents. Primary outcomes were percent changes in CRP, ferritin, homocysteine, WBC count, and anti-TPO antibody levels. CRP levels decreased by 33\u201346% across all groups, with similarly consistent declines in homocysteine (29\u201337%) and WBC count (22\u201328%). Ferritin reductions were most notable in men, particularly in older age groups (up to 48%), while anti-TPO antibody levels declined more prominently in women (up to 22%). These changes are consistent with reduced systemic inflammation, improved methylation status, and potential modulation of autoimmune activity. This biomarker-guided, personalized supplementation protocol was associated with clinically meaningful reductions in key markers of inflammation and immune dysregulation. These findings are suggestive of potential efficacy for precision-based health optimization programs and highlight the need for larger randomized controlled trials (RCTs) to confirm causal effects.<\/jats:p>","DOI":"10.3390\/life15121887","type":"journal-article","created":{"date-parts":[[2025,12,10]],"date-time":"2025-12-10T12:20:57Z","timestamp":1765369257000},"page":"1887","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Personalized Supplementation Is Associated with Reduced Inflammatory Biomarkers: A 12-Week Observational Study"],"prefix":"10.3390","volume":"15","author":[{"given":"Eliza","family":"Roeth","sequence":"first","affiliation":[{"name":"Department of Cell Biology and Physiology, Brigham Young University, Provo, UT 84602, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Madeline","family":"Morris","sequence":"additional","affiliation":[{"name":"Department of Cell Biology and Physiology, Brigham Young University, Provo, UT 84602, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Asher P.","family":"Reynolds","sequence":"additional","affiliation":[{"name":"Department of Cell Biology and Physiology, Brigham Young University, Provo, UT 84602, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emma M.","family":"Reynolds","sequence":"additional","affiliation":[{"name":"Department of Cell Biology and Physiology, Brigham Young University, Provo, UT 84602, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reed","family":"Hungerford","sequence":"additional","affiliation":[{"name":"Department of Cell Biology and Physiology, Brigham Young University, Provo, UT 84602, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eliza J.","family":"Livingston","sequence":"additional","affiliation":[{"name":"Department of Cell Biology and Physiology, Brigham Young University, Provo, UT 84602, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew W.","family":"Richardson","sequence":"additional","affiliation":[{"name":"Department of Cell Biology and Physiology, Brigham Young University, Provo, UT 84602, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin T.","family":"Bikman","sequence":"additional","affiliation":[{"name":"Department of Cell Biology and Physiology, Brigham Young University, Provo, UT 84602, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0931-3025","authenticated-orcid":false,"given":"Paul R.","family":"Reynolds","sequence":"additional","affiliation":[{"name":"Department of Cell Biology and Physiology, Brigham Young University, Provo, UT 84602, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e2294","DOI":"10.1212\/WNL.0000000000201116","article-title":"Association of Midlife Inflammatory Markers With Cognitive Performance at 10-Year Follow-up","volume":"99","author":"Kipinoinen","year":"2022","journal-title":"Neurology"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"595","DOI":"10.3899\/jrheum.110006","article-title":"Low-grade chronic inflammation and vascular damage in patients with rheumatoid arthritis: Don\u2019t forget \u201cmetabolic inflammation\u201d","volume":"38","author":"Jeppesen","year":"2011","journal-title":"J. Rheumatol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1016\/S0939-4753(04)80048-6","article-title":"The metabolic syndrome and inflammation: Association or causation?","volume":"14","author":"Esposito","year":"2004","journal-title":"Nutr. Metab. Cardiovasc. Dis."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Zotova, N., Zhuravleva, Y., Chereshnev, V., and Gusev, E. (2023). Acute and Chronic Systemic Inflammation: Features and Differences in the Pathogenesis, and Integral Criteria for Verification and Differentiation. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24021144"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Del Pinto, R., and Ferri, C. (2018). Inflammation-Accelerated Senescence and the Cardiovascular System: Mechanisms and Perspectives. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19123701"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1159\/000356535","article-title":"Chronic low-grade inflammation in metabolic disorders: Relevance for behavioral symptoms","volume":"21","author":"Lasselin","year":"2014","journal-title":"Neuroimmunomodulation"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"244","DOI":"10.1016\/j.numecd.2010.06.001","article-title":"Chronic inflammation is associated with overweight in Colombian school children","volume":"22","author":"Baylin","year":"2012","journal-title":"Nutr. Metab. Cardiovasc. Dis."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Cramer, D.W., and Vitonis, A.F. (2017). Signatures of reproductive events on blood counts and biomarkers of inflammation: Implications for chronic disease risk. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0172530"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Haghbin, M., Razmjooei, F., Abbasi, F., Rouhie, R., Pourabbas, P., Mir, H., Roustazadeh, A., Mofazzal Jahromi, M.A., and Bagheri, K. (2024). Evaluation of the hematological parameters, inflammatory biomarkers, and thyroid hormones in hypothyroidism patients. BMC Res. Notes, 17.","DOI":"10.1186\/s13104-024-07048-4"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Walentukiewicz, A., Lysak-Radomska, A., Jaworska, J., Prusik, K., Prusik, K., Kortas, J.A., Lipi\u0144ski, M., Babinska, A., Antosiewicz, J., and Ziemann, E. (2018). Vitamin D Supplementation and Nordic Walking Training Decreases Serum Homocysteine and Ferritin in Elderly Women. Int. J. Environ. Res. Public Health, 15.","DOI":"10.3390\/ijerph15102064"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Pereira, S.L., Shoemaker, M.E., Gawel, S., Davis, G.J., Luo, M., Mustad, V.A., and Cramer, J.T. (2022). Biomarker Changes in Response to a 12-Week Supplementation of an Oral Nutritional Supplement Enriched with Protein, Vitamin D and HMB in Malnourished Community Dwelling Older Adults with Sarcopenia. Nutrients, 14.","DOI":"10.3390\/nu14061196"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Ooi, T.C., Ahmad, A., Rajab, N.F., and Sharif, R. (2023). The Effects of 12 Weeks Colostrum Milk Supplementation on the Expression Levels of Pro-Inflammatory Mediators and Metabolic Changes among Older Adults: Findings from the Biomarkers and Untargeted Metabolomic Analysis. Nutrients, 15.","DOI":"10.3390\/nu15143184"},{"key":"ref_13","first-page":"e92449","article-title":"Effects of 12-Week Multiple Micronutrient Supplementation on Immune Function, Body Weight, and Metabolic Parameters in Middle-Aged Women: A Retrospective Study","volume":"17","author":"Sun","year":"2025","journal-title":"Cureus"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1038\/s41569-018-0064-2","article-title":"Inflammageing: Chronic inflammation in ageing, cardiovascular disease, and frailty","volume":"15","author":"Ferrucci","year":"2018","journal-title":"Nat. Rev. Cardiol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1822","DOI":"10.1038\/s41591-019-0675-0","article-title":"Chronic inflammation in the etiology of disease across the life span","volume":"25","author":"Furman","year":"2019","journal-title":"Nat. Med."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"S4","DOI":"10.1093\/gerona\/glu057","article-title":"Chronic inflammation (inflammaging) and its potential contribution to age-associated diseases","volume":"69","author":"Franceschi","year":"2014","journal-title":"J. Gerontol. A Biol. Sci. Med. Sci."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1128","DOI":"10.1111\/j.1538-7836.2007.02528.x","article-title":"Inflammation and hemostasis biomarkers and cardiovascular risk in the elderly: The Cardiovascular Health Study","volume":"5","author":"Zakai","year":"2007","journal-title":"J. Thromb. Haemost."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"109104","DOI":"10.1016\/j.intimp.2022.109104","article-title":"Efficacy of the omega-3 fatty acids supplementation on inflammatory biomarkers: An umbrella meta-analysis","volume":"111","author":"Kavyani","year":"2022","journal-title":"Int. Immunopharmacol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"e6179","DOI":"10.1097\/MD.0000000000006179","article-title":"Association of serum ferritin with insulin resistance, abdominal obesity, and metabolic syndrome in Korean adolescent and adults: The Korean National Health and Nutrition Examination Survey, 2008 to 2011","volume":"96","author":"Shim","year":"2017","journal-title":"Medicine"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1159\/000437098","article-title":"Homocysteine-Induced Endothelial Dysfunction","volume":"67","author":"Lai","year":"2015","journal-title":"Ann. Nutr. Metab."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1236","DOI":"10.1139\/Y07-112","article-title":"Homocysteine stimulates NADPH oxidase-mediated superoxide production leading to endothelial dysfunction in rats","volume":"85","author":"Edirimanne","year":"2007","journal-title":"Can. J. Physiol. Pharmacol."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Chatterjee, B., Fatima, F., Seth, S., and Sinha Roy, S. (2024). Moderate Elevation of Homocysteine Induces Endothelial Dysfunction through Adaptive UPR Activation and Metabolic Rewiring. Cells, 13.","DOI":"10.3390\/cells13030214"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1001\/archinte.164.4.433","article-title":"Predictive value of elevated white blood cell count in patients with preexisting coronary heart disease: The Bezafibrate Infarction Prevention Study","volume":"164","author":"Haim","year":"2004","journal-title":"Arch. Intern. Med."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"500","DOI":"10.1001\/archinte.165.5.500","article-title":"Leukocyte count as a predictor of cardiovascular events and mortality in postmenopausal women: The Women\u2019s Health Initiative Observational Study","volume":"165","author":"Margolis","year":"2005","journal-title":"Arch. Intern. Med."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1415","DOI":"10.1161\/ATVBAHA.118.310945","article-title":"Association of Total and Differential Leukocyte Counts With Cardiovascular Disease and Mortality in the UK Biobank","volume":"38","author":"Welsh","year":"2018","journal-title":"Arter. Thromb. Vasc. Biol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"739","DOI":"10.1046\/j.1365-2141.2003.04354.x","article-title":"Growth regulation by p27Kip1 is abrogated by multiple mechanisms in aggressive malignant lymphomas","volume":"121","author":"Lin","year":"2003","journal-title":"Br. J. Haematol."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Pokushalov, E., Ponomarenko, A., Shrainer, E., Kudlay, D., and Miller, R. (2024). Biomarker-Guided Dietary Supplementation: A Narrative Review of Precision in Personalized Nutrition. Nutrients, 16.","DOI":"10.3390\/nu16234033"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1041","DOI":"10.1016\/j.clnu.2024.03.006","article-title":"Probiotics and synbiotics for glycemic control in diabetes: A systematic review and meta-analysis of randomized controlled trials","volume":"43","author":"Baroni","year":"2024","journal-title":"Clin. Nutr."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"afaf269","DOI":"10.1093\/ageing\/afaf269","article-title":"Effects of 2-year cocoa extract supplementation on inflammaging biomarkers in older US adults: Findings from the COcoa Supplement and Multivitamin Outcomes Study randomised clinical trial","volume":"54","author":"Li","year":"2025","journal-title":"Age Ageing"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Wang, X., Sun, Z., Xue, H., and An, R. (2025). Artificial Intelligence Applications to Personalized Dietary Recommendations: A Systematic Review. Healthcare, 13.","DOI":"10.3390\/healthcare13121417"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"100398","DOI":"10.1016\/j.advnut.2025.100398","article-title":"A Scoping Review of Artificial Intelligence for Precision Nutrition","volume":"16","author":"Wu","year":"2025","journal-title":"Adv. Nutr."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"171","DOI":"10.14715\/cmb\/2024.70.6.26","article-title":"Effect of omega-3 fatty acid supplementation on markers of inflammation and endothelial function in patients with chronic heart disease: A systematic review and meta-analysis","volume":"70","author":"Gubari","year":"2024","journal-title":"Cell. Mol. Biol."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Liu, H., Zhang, L., Yu, J., and Shao, S. (2024). Advances in the application and mechanism of bioactive peptides in the treatment of inflammation. Front. Immunol., 15.","DOI":"10.3389\/fimmu.2024.1413179"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"204","DOI":"10.3390\/muscles2020015","article-title":"MSM Supplementation Is Associated with Reduced Inflammation and Improved Innate Immune Response following In Vitro LPS-Stimulation in Humans after a Bout of Downhill Running","volume":"2","author":"McFarlin","year":"2023","journal-title":"Muscles"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Singar, S., Nagpal, R., Arjmandi, B.H., and Akhavan, N.S. (2024). Personalized Nutrition: Tailoring Dietary Recommendations through Genetic Insights. Nutrients, 16.","DOI":"10.3390\/nu16162673"},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Agrawal, K., Goktas, P., Kumar, N., and Leung, M.F. (2025). Artificial intelligence in personalized nutrition and food manufacturing: A comprehensive review of methods, applications, and future directions. Front. Nutr., 12.","DOI":"10.3389\/fnut.2025.1636980"}],"container-title":["Life"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2075-1729\/15\/12\/1887\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,12]],"date-time":"2025-12-12T05:22:53Z","timestamp":1765516973000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2075-1729\/15\/12\/1887"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12,10]]},"references-count":36,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["life15121887"],"URL":"https:\/\/doi.org\/10.3390\/life15121887","relation":{},"ISSN":["2075-1729"],"issn-type":[{"value":"2075-1729","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,12,10]]}}}