{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T01:21:31Z","timestamp":1792718491306,"version":"4.5.0"},"reference-count":43,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,7,24]],"date-time":"2025-07-24T00:00:00Z","timestamp":1753315200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Nutr."],"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>Diabetic nephropathy (DN) poses significant health risks and imposes a substantial global disease burden. The association between carotenoid intake and DN remains unclear. Utilizing data from the 2007\u20132018 National Health and Nutrition Examination Survey (NHANES), this study investigates the relationship between multiple carotenoid subtypes and DN, aiming to inform exploratory insights for potential preventive strategies.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>This cross-sectional analysis utilized NHANES 2007\u20132018 data with a multistage stratified sampling design. After a four-stage screening process, baseline participants were selected by excluding individuals with lacking diabetes-related data, pregnant women, and those with incomplete carotenoid intake or DN diagnostic records. Model 1 included 25,483 participants, while Model 2 comprised retained 13,271 participants after further adjustment for covariates (demographic characteristics, lifestyle factors, clinical indicators, and socioeconomic parameters). Dietary intake of six carotenoid subtypes (<jats:italic>\u03b1-carotene, \u03b2-carotene, \u03b2-cryptoxanthin, Lycopene, Lutein, Zeaxanthin<\/jats:italic>) was calculated using as the mean of two standardized 24-h dietary recalls. Type 2 diabetes mellitus (T2DM) was diagnosed based on fasting plasma glucose (\u2265126\u202fmg\/dL), HbA1c (\u22656.5%), hypoglycemic medication use, or clinical diagnosis. DN was defined as a urinary albumin-to-creatinine ratio (UACR)\u202f\u2265\u202f30\u202fmg\/g or estimated glomerular filtration rate (eGFR)\u202f&amp;lt;\u202f60\u202fmL\/min\/1.73\u202fm<jats:sup>2<\/jats:sup> in T2DM patients. Statistical analyses employed weighted multivariable logistic regression using the R survey package, adjusting for sampling design and covariates. Associations were quantified as odds ratios (ORs per 10\u202f\u03bcg\/d carotenoid intake) with Benjamini-Hochberg correction for multiple comparisons. The significance threshold was set at <jats:italic>\u03b1<\/jats:italic>\u202f=\u202f0.05.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>This NHANES-based study revealed nonlinear associations between dietary carotenoids and diabetic nephropathy (DN) risk, with notable gender-and ethnicity-specific gender\/ethnicity-specific effects. Univariate analysis demonstrated elevated DN risk with higher \u03b2-cryptoxanthin intake (OR\u202f=\u202f1.413, 95% CI), though significance was attenuated dissipated after multivariable adjustment, suggesting confounding mediation by obesity and hypertension. Multivariable models identified threshold effects: the low <jats:italic>\u03b1<\/jats:italic>-carotene intake group exhibited a 75% reduced risk (OR\u202f=\u202f0.25, 95% CI), while the high-intake group showed a paradoxical risk elevation (OR\u202f=\u202f2.24, 95% CI). \u03b2-Carotene displayed gender-divergent effects, with the highest tertile significantly reducing risk in males by 43% (OR\u202f=\u202f0.57, 95% CI). Interaction models highlighted intensified <jats:italic>\u03b1<\/jats:italic>-carotene protection in males and Non-Hispanic White (OR = 0.27\u20130.29), whereas lycopene correlated with a fivefold increased DN risk in Non-Hispanic Black (OR\u202f=\u202f4.99, 95% CI). Cardinal risk factors included advanced age (OR\u202f=\u202f1.06\/year), obesity (OR\u202f=\u202f1.07\/BMI unit), male sex (OR\u202f=\u202f3.05), and hypertension (OR\u202f=\u202f4.7), while higher education (OR\u202f=\u202f0.72) and moderate alcohol consumption exerted inversely associated effects. These findings underscore the necessity of integrating nutrient thresholds (e.g., <jats:italic>\u03b1<\/jats:italic>-carotene optimization) and social determinants into DN prevention, though racial subgroup analyses warrant validation through prospective cohorts due to sample size constraints.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Clinicians managing DN should: Prioritize Consider <jats:italic>\u03b1<\/jats:italic>-carotene\u2019s biphasic dose\u2013response relationship, prioritizing intake within the optimal dosage window; Utilize Leverage \u03b2-carotene\u2019s gender-specific benefits for male patients; Exercise caution in consider exploringing lycopene-rich dietary interventions diets for African American populations. Public health initiatives should incorporate nutrient-gender-ethnicity triadic assessments into DN education programs to advance precision nutrition guidelines.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fnut.2025.1584692","type":"journal-article","created":{"date-parts":[[2025,7,24]],"date-time":"2025-07-24T14:24:15Z","timestamp":1753367055000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["The relationship between carotenoids and diabetic nephropathy: insights from NHANES"],"prefix":"10.3389","volume":"12","author":[{"given":"Lei","family":"Wang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tianpu","family":"Feng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ye","family":"Tan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jue","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ting","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan","family":"Huo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"XiaoXue","family":"Song","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xi","family":"Lin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Man","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenxue","family":"Liang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qun","family":"Ding","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,7,24]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"S191","DOI":"10.2337\/dc23-s011","article-title":"11. Chronic kidney disease and risk management: standards of care in diabetes\u20142023","volume":"46","author":"Elsayed","year":"2023","journal-title":"Diabetes Care"},{"key":"ref2","volume-title":"2021 USRDS annual data report: epidemiology of kidney disease in the United States","year":"2021"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"3075","DOI":"10.2337\/dci22-0027","article-title":"Diabetes management in chronic kidney disease: a consensus report by the American Diabetes Association (ADA) and kidney disease: improving global outcomes (KDIGO)","volume":"45","author":"de Boer","year":"2022","journal-title":"Kidney Int"},{"key":"ref4","doi-asserted-by":"publisher","first-page":"20","DOI":"10.1038\/kisup.2014.5","article-title":"Toll-like receptor activation: from renal inflammation to fibrosis","volume":"4","author":"Wai Han","year":"2011","journal-title":"Kidney Int Suppl"},{"key":"ref5","doi-asserted-by":"publisher","first-page":"884","DOI":"10.1001\/jama.2015.10081","article-title":"Effect of finerenone on albuminuria in patients with diabetic nephropathy: a randomized clinical trial","volume":"314","author":"Bakris","year":"2015","journal-title":"JAMA"},{"key":"ref6","doi-asserted-by":"publisher","first-page":"1108","DOI":"10.1681\/ASN.2017060627","article-title":"The adiponectin receptor agonist AdipoRon ameliorates diabetic nephropathy in a model of type 2 diabetes","volume":"29","author":"Kim","year":"2018","journal-title":"J Am Soc Nephrol"},{"key":"ref7","doi-asserted-by":"publisher","first-page":"e2100784","DOI":"10.1002\/mnfr.202100784","article-title":"Dietary blueberry ameliorates vascular complications in diabetic mice possibly through NOX4 and modulates composition and functional diversity of gut microbes","volume":"66","author":"Petersen","year":"2022","journal-title":"Mol Nutr Food Res"},{"key":"ref8","doi-asserted-by":"publisher","first-page":"3025","DOI":"10.1002\/fsn3.3983","article-title":"Dietary phenolic compounds as promising therapeutic agents for diabetes and its complications: a comprehensive review","volume":"12","author":"Aryal","year":"2024","journal-title":"Food Sci Nutr"},{"key":"ref9","doi-asserted-by":"publisher","first-page":"14","DOI":"10.3945\/an.115.009803","article-title":"Potential of dietary non-Provitamin a carotenoids in the prevention and treatment of diabetic microvascular complications","volume":"7","author":"Murillo","year":"2016","journal-title":"Adv Nutr"},{"key":"ref10","doi-asserted-by":"publisher","first-page":"345","DOI":"10.1016\/s0098-2997(03)00030-x","article-title":"Antioxidant activity of carotenoids","volume":"24","author":"Stahl","year":"2003","journal-title":"Mol Asp Med"},{"key":"ref11","doi-asserted-by":"publisher","first-page":"11206","DOI":"10.1080\/10408398.2023.2234025","article-title":"Effect of carotenoids on gut health and inflammatory status: a systematic review of in vivo animal studies","volume":"64","author":"Meneguelli","year":"2024","journal-title":"Crit Rev Food Sci Nutr"},{"key":"ref12","doi-asserted-by":"publisher","first-page":"1069","DOI":"10.1093\/ajcn\/nqy097","article-title":"Dietary intake and blood concentrations of antioxidants and the risk of cardiovascular disease, total cancer, and all-cause mortality: a systematic review and dose-response meta-analysis of prospective studies","volume":"108","author":"Aune","year":"2018","journal-title":"Am J Clin Nutr"},{"key":"ref13","doi-asserted-by":"publisher","first-page":"159604","DOI":"10.1016\/j.bbalip.2025.159604","article-title":"Preventive effect of siphonaxanthin, a carotenoid from green algae, against diabetic nephropathy and lipid metabolism insufficiency in skeletal muscle","volume":"1870","author":"Zheng","year":"2025","journal-title":"Biochim Biophys Acta Mol Cell Biol Lipids"},{"key":"ref14","doi-asserted-by":"publisher","first-page":"105","DOI":"10.1002\/biof.5520200105","article-title":"Prevention of diabetic nephropathy by treatment with astaxanthin in diabetic db\/db mice","volume":"32","author":"Naito","year":"2008","journal-title":"Biofactors"},{"key":"ref15","doi-asserted-by":"publisher","first-page":"1340","DOI":"10.1016\/j.jand.2019.03.009","article-title":"Hyperglycemia and carotenoid intake are associated with serum carotenoids in youth with type 1 diabetes","volume":"119","author":"Sanjeevi","year":"2019","journal-title":"J Acad Nutr Diet"},{"key":"ref16","doi-asserted-by":"publisher","first-page":"850","DOI":"10.1053\/j.ajkd.2012.07.005","article-title":"KDOQI clinical practice guideline for diabetes and CKD: 2012 update","volume":"60","year":"2012","journal-title":"Am J Kidney Dis"},{"key":"ref17","doi-asserted-by":"publisher","first-page":"1365","DOI":"10.1007\/s00592-023-02125-9","article-title":"Dose-response relationship between dietary antioxidant intake and diabetic kidney disease in the US adults with diabetes","volume":"60","author":"Zhang","year":"2023","journal-title":"Acta Diabetol"},{"key":"ref18","first-page":"16","article-title":"Crit\u00e8res diagnostiques du diab\u00e8te de type 2 [Diagnostic criteria for type 2 diabetes]","volume":"49","author":"Grimaldi","year":"1999","journal-title":"Rev Prat"},{"key":"ref19","volume-title":"Dietary guidelines for Americans, 2020\u20132025","year":"2020"},{"key":"ref20","doi-asserted-by":"publisher","first-page":"3912","DOI":"10.1093\/eurheartj\/ehae178","article-title":"2024 ESC guidelines for the management of elevated blood pressure and hypertension","volume":"45","author":"McEvoy","year":"2024","journal-title":"Eur Heart J"},{"key":"ref21","year":"2024"},{"key":"ref22","doi-asserted-by":"publisher","first-page":"121","DOI":"10.3945\/an.115.009258","article-title":"Update on NHANES dietary data: focus on collection, release, analytical considerations, and uses to inform public policy","volume":"7","author":"Ahluwalia","year":"2016","journal-title":"Adv Nutr"},{"key":"ref23","doi-asserted-by":"publisher","first-page":"120755","DOI":"10.1016\/j.saa.2021.120755","article-title":"Relations between the Raman spectra and molecular structure of selected carotenoids: DFT study of \u03b1-carotene, \u03b2-carotene, \u03b3-carotene and lycopene","volume":"270","author":"Novikov","year":"2022","journal-title":"Spectrochim Acta A Mol Biomol Spectrosc"},{"key":"ref24","doi-asserted-by":"publisher","first-page":"1613","DOI":"10.3390\/antiox11081613","article-title":"Hormesis and oxidative distress: pathophysiology of reactive oxygen species and the open question of antioxidant modulation and supplementation","volume":"11","author":"Nitti","year":"2022","journal-title":"Antioxidants"},{"key":"ref25","volume-title":"Global report on diabetes","year":"2016"},{"key":"ref26","doi-asserted-by":"publisher","first-page":"614","DOI":"10.3390\/nu8100614","article-title":"Plasma carotenoids, tocopherols, and retinol in the age-stratified (35\u201374 years) general population: a cross-sectional study in six European countries","volume":"8","author":"Stuetz","year":"2016","journal-title":"Nutrients"},{"key":"ref27","doi-asserted-by":"publisher","first-page":"1116","DOI":"10.1111\/tpj.15498","article-title":"DcCCD4 catalyzes the degradation of \u03b1-carotene and \u03b2-carotene to affect carotenoid accumulation and taproot color in carrot","volume":"4","author":"Li","year":"2021","journal-title":"Plant J"},{"key":"ref28","doi-asserted-by":"publisher","first-page":"40","DOI":"10.1093\/jn\/nxab340","article-title":"The plasma proteome fingerprint associated with circulatingcarotenoids and retinol in older adults","volume":"152","author":"Yamaguchi","year":"2021","journal-title":"J Nutr"},{"key":"ref29","doi-asserted-by":"publisher","first-page":"e2100650","DOI":"10.1002\/mnfr.202100650","article-title":"\u0392-Carotene bioavailability and conversion efficiency are significantly affected by sex in rats: first observation suggesting a possible hormetic regulation of vitamin a metabolism in female rats","volume":"65","author":"Borel","year":"2021","journal-title":"Mol Nutr Food Res"},{"key":"ref30","doi-asserted-by":"publisher","first-page":"35","DOI":"10.1146\/annurev-nutr-080508-141027","article-title":"Colors with functions: elucidating the biochemical and molecular basis of carotenoid metabolism","volume":"30","author":"Von Lintig","year":"2010","journal-title":"Annu Rev Nutr"},{"key":"ref31","doi-asserted-by":"publisher","first-page":"4457","DOI":"10.1096\/fj.14-252411","article-title":"Evidence for compartmentalization of mammalian carotenoid metabolism","volume":"28","author":"Palczewski","year":"2014","journal-title":"FASEB J"},{"key":"ref32","doi-asserted-by":"publisher","first-page":"309","DOI":"10.1210\/er.2012-1055","article-title":"The role of estrogens in control of energy balance and glucose homeostasis","volume":"34","author":"Mauvais-Jarvis","year":"2013","journal-title":"Endocr Rev"},{"key":"ref33","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1016\/j.molmet.2018.05.008","article-title":"Sex differences in lipid and lipoprotein metabolism","volume":"15","author":"Palmisano","year":"2018","journal-title":"Mol Metab"},{"key":"ref34","doi-asserted-by":"publisher","first-page":"e12208","DOI":"10.1002\/trc2.12208","article-title":"Plasma antioxidants and risk of dementia in older adults","volume":"7","author":"Koch","year":"2021","journal-title":"Alzheimers Dement"},{"key":"ref35","doi-asserted-by":"publisher","first-page":"101461","DOI":"10.1016\/j.redox.2020.101461","article-title":"Plasma carotenoids, tocopherols and retinol-association with age in the Berlin aging study II","volume":"32","author":"Weber","year":"2020","journal-title":"Redox Biol"},{"key":"ref36","doi-asserted-by":"publisher","first-page":"438","DOI":"10.3390\/ijms20020438","article-title":"Gut microbiota and predicted metabolic pathways in a sample of Mexican women affected by obesity and obesity plus metabolic syndrome","volume":"20","author":"Ch\u00e1vez-Carbajal","year":"2019","journal-title":"Int J Mol Sci"},{"key":"ref37","doi-asserted-by":"publisher","first-page":"773","DOI":"10.4251\/wjgo.v11.i10.773","article-title":"Race, the microbiome and colorectal cancer","volume":"11","author":"Royston","year":"2019","journal-title":"World J Gastrointest Oncol"},{"key":"ref38","doi-asserted-by":"publisher","first-page":"2392","DOI":"10.2337\/diacare.26.8.2392","article-title":"Racial differences in diabetic nephropathy, cardiovascular disease, and mortality in a national population of veterans","volume":"26","author":"Young","year":"2003","journal-title":"Diabetes Care"},{"key":"ref39","doi-asserted-by":"publisher","first-page":"455","DOI":"10.1007\/s11892-004-0056-y","article-title":"Diabetic nephropathy in African-American patients","volume":"4","author":"Crook","year":"2004","journal-title":"Curr Diab Rep"},{"key":"ref40","doi-asserted-by":"publisher","first-page":"916","DOI":"10.2105\/ajph.2017.303815","article-title":"Overview of Asian American data collection, release, and analysis: National Health and nutrition examination survey 2011\u20132018","volume":"107","author":"Paulose-Ram","year":"2017","journal-title":"Am J Public Health"},{"key":"ref41","doi-asserted-by":"publisher","first-page":"281","DOI":"10.1038\/s41575-024-01022-y","article-title":"The steatotic liver disease burden paradox: unravelling the key role of alcohol","volume":"22","author":"Torp","year":"2024","journal-title":"Nat Rev Gastroenterol Hepatol"},{"key":"ref42","doi-asserted-by":"publisher","first-page":"3168","DOI":"10.1016\/j.clnu.2020.02.009","article-title":"Drink types unmask the health risks associated with alcohol intake \u2013 prospective evidence from the general population","volume":"39","author":"Schutte","year":"2020","journal-title":"Clin Nutr"},{"key":"ref43","doi-asserted-by":"publisher","first-page":"280","DOI":"10.1046\/j.1365-2796.2003.01268.x","article-title":"Is the relationship between type of alcohol and mortality influenced by socio-economic status?","volume":"255","author":"Nielsen","year":"2004","journal-title":"J Intern Med"}],"container-title":["Frontiers in Nutrition"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnut.2025.1584692\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,7,24]],"date-time":"2025-07-24T14:24:17Z","timestamp":1753367057000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnut.2025.1584692\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7,24]]},"references-count":43,"alternative-id":["10.3389\/fnut.2025.1584692"],"URL":"https:\/\/doi.org\/10.3389\/fnut.2025.1584692","relation":{},"ISSN":["2296-861X"],"issn-type":[{"value":"2296-861X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,7,24]]},"article-number":"1584692"}}