{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,27]],"date-time":"2026-05-27T19:42:16Z","timestamp":1779910936754,"version":"3.53.1"},"reference-count":64,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,9,11]],"date-time":"2025-09-11T00:00:00Z","timestamp":1757548800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003453","name":"Natural Science Foundation of Guangdong Province","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003453","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Nutr."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Methylenetetrahydrofolate reductase (MTHFR) regulates folate metabolism and homocysteine (Hcy) methylation. Impaired folate metabolism and vitamin D deficiency are both closely associated with female reproductive disorders, but their specific roles and relationship remain largely unknown. This study aimed to investigate the relationship between MTHFR polymorphisms and vitamin D status and to examine the mediating effect of Hcy.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A total of 6,344 infertile patients were included in this retrospective study. Multivariable logistic regression and multiple linear regression models, and stratified analyses were used to investigate the relationship between MTHFR polymorphisms (C677T and A1298C) and vitamin D status. Smooth curve fitting model and spearman correlation analysis were used to explore the correlation between Hcy levels and vitamin D status. Mediation analyses were performed to examine the direct and indirect effects of MTHFR polymorphisms on vitamin D status.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The risk of vitamin D deficiency and serum Hcy levels were significantly higher in patients with MTHFR677CT and TT compared with CC (<jats:italic>p<\/jats:italic>\u202f&amp;lt;\u202f0.001 for both). In multivariate regression models, MTHFR677CT and TT were positively associated with vitamin D deficiency compared with CC. No significant differences were found for A1298C polymorphism. Smooth curve fitting models showed that serum Hcy was linearly correlated with both 25(OH)D levels (<jats:italic>p<\/jats:italic>-nonlinear\u202f=\u202f0.063) and prevalence of vitamin D deficiency (<jats:italic>p<\/jats:italic>-nonlinear\u202f=\u202f0.261). In mediation analyses using logistic regression models, Hcy mediated 15.8 and 41.6% of the associations between 677CT and TT (versus CC) and vitamin D deficiency, respectively.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The effect of C677T polymorphism on vitamin D status can be explained jointly by a direct association between C677T polymorphism and vitamin D, and an indirect association mediated by Hcy.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fnut.2025.1644302","type":"journal-article","created":{"date-parts":[[2025,9,11]],"date-time":"2025-09-11T04:12:58Z","timestamp":1757563978000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Association between MTHFR polymorphisms and vitamin D status in infertile women: a mediation analysis"],"prefix":"10.3389","volume":"12","author":[{"given":"Ruiqiong","family":"Zhou","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenghong","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhaoyi","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mei","family":"Dong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Songlu","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiqian","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fenghua","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,9,11]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"755","DOI":"10.3945\/an.112.002758","article-title":"Homocysteine imbalance: a pathological metabolic marker","volume":"3","author":"Schalinske","year":"2012","journal-title":"Advances Nutr"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"551","DOI":"10.1038\/ng0894-551a","article-title":"Human methylenetetrahydrofolate reductase: isolation of cDNA mapping and mutation identification","volume":"7","author":"Goyette","year":"1994","journal-title":"Nat Genet"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"111","DOI":"10.1038\/ng0595-111","article-title":"A candidate genetic risk factor for vascular disease: a common mutation in methylenetetrahydrofolate reductase","volume":"10","author":"Frosst","year":"1995","journal-title":"Nat Genet"},{"key":"ref4","first-page":"142","article-title":"Thermolabile 5,10-methylenetetrahydrofolate reductase as a cause of mild hyperhomocysteinemia","volume":"56","author":"Engbersen","year":"1995","journal-title":"Am J Hum Genet"},{"key":"ref5","doi-asserted-by":"publisher","first-page":"1044","DOI":"10.1086\/301825","article-title":"A second common mutation in the methylenetetrahydrofolate reductase gene: an additional risk factor for neural-tube defects?","volume":"62","author":"van der Put","year":"1998","journal-title":"Am J Hum Genet"},{"key":"ref6","doi-asserted-by":"publisher","first-page":"46","DOI":"10.1093\/ajcn\/65.1.46","article-title":"Folate deficiency in rats induces DNA strand breaks and hypomethylation within the p53 tumor suppressor gene","volume":"65","author":"Kim","year":"1997","journal-title":"Am J Clin Nutr"},{"key":"ref7","doi-asserted-by":"publisher","first-page":"433","DOI":"10.1093\/hmg\/10.5.433","article-title":"Mice deficient in methylenetetrahydrofolate reductase exhibit hyperhomocysteinemia and decreased methylation capacity, with neuropathology and aortic lipid deposition","volume":"10","author":"Chen","year":"2001","journal-title":"Hum Mol Genet"},{"key":"ref8","doi-asserted-by":"publisher","first-page":"48","DOI":"10.1093\/jn\/134.1.48","article-title":"Methylenetetrahydrofolate reductase C677T polymorphism, folic acid and riboflavin are important determinants of genome stability in cultured human lymphocytes","volume":"134","author":"Kimura","year":"2004","journal-title":"J Nutr"},{"key":"ref9","doi-asserted-by":"publisher","first-page":"1204","DOI":"10.1093\/jn\/128.7.1204","article-title":"Moderate folate depletion increases plasma homocysteine and decreases lymphocyte DNA methylation in postmenopausal women","volume":"128","author":"Jacob","year":"1998","journal-title":"J Nutr"},{"key":"ref10","first-page":"849","article-title":"Genomic DNA hypomethylation, a characteristic of most cancers, is present in peripheral leukocytes of individuals who are homozygous for the C677T polymorphism in the methylenetetrahydrofolate reductase gene","volume":"9","author":"Stern","year":"2000","journal-title":"Cancer Epidemiol Biomarkers Prevent"},{"key":"ref11","doi-asserted-by":"publisher","first-page":"5606","DOI":"10.1073\/pnas.062066299","article-title":"A common mutation in the 5,10-methylenetetrahydrofolate reductase gene affects genomic DNA methylation through an interaction with folate status","volume":"99","author":"Friso","year":"2002","journal-title":"Proc Natl Acad Sci USA"},{"key":"ref12","doi-asserted-by":"publisher","first-page":"454","DOI":"10.1136\/jmg.2003.017244","article-title":"5,10-methylenetetrahydrofolate reductase (MTHFR) 677C->T and 1298A->C mutations are associated with DNA hypomethylation","volume":"41","author":"Castro","year":"2004","journal-title":"J Med Genet"},{"key":"ref13","doi-asserted-by":"publisher","first-page":"861","DOI":"10.1016\/S0140-6736(97)24038-9","article-title":"Genetic risk factor for unexplained recurrent early pregnancy loss","volume":"350","author":"Nelen","year":"1997","journal-title":"Lancet (London, England)"},{"key":"ref14","doi-asserted-by":"publisher","first-page":"210","DOI":"10.1177\/1933719111417888","article-title":"MTHFR C677T polymorphism and recurrent early pregnancy loss risk in north Indian population","volume":"19","author":"Nair","year":"2012","journal-title":"Reproduct Sci"},{"key":"ref15","doi-asserted-by":"publisher","first-page":"283","DOI":"10.1007\/s00404-015-3894-8","article-title":"Methylenetetrahydrofolate reductase gene polymorphisms and recurrent pregnancy loss in China: a systematic review and meta-analysis","volume":"293","author":"Chen","year":"2016","journal-title":"Arch Gynecol Obstet"},{"key":"ref16","doi-asserted-by":"publisher","first-page":"597","DOI":"10.1016\/j.fertnstert.2018.11.011","article-title":"Relationship between unexplained recurrent pregnancy loss and 5,10-methylenetetrahydrofolate reductase polymorphisms","volume":"111","author":"Xu","year":"2019","journal-title":"Fertil Steril"},{"key":"ref17","doi-asserted-by":"publisher","first-page":"6670","DOI":"10.3390\/nu7085303","article-title":"Homocysteine metabolism gene polymorphisms (MTHFR C677T, MTHFR A1298C, MTR A2756G and MTRR A66G) jointly elevate the risk of folate deficiency","volume":"7","author":"Li","year":"2015","journal-title":"Nutrients"},{"key":"ref18","doi-asserted-by":"publisher","first-page":"919651","DOI":"10.3389\/fnut.2022.919651","article-title":"Polymorphisms in gene MTHFR modify the association between gestational weight gain and adverse birth outcomes","volume":"9","author":"Wu","year":"2022","journal-title":"Front Nutr"},{"key":"ref19","doi-asserted-by":"publisher","first-page":"295","DOI":"10.1186\/s12884-023-05605-6","article-title":"Maternal pre-pregnancy BMI, MTHFR polymorphisms, and the risk of adverse pregnancy outcomes in pregnant women from South China: a retrospective cohort study","volume":"23","author":"Gu","year":"2023","journal-title":"BMC Pregnancy Childbirth"},{"key":"ref20","doi-asserted-by":"publisher","first-page":"1513","DOI":"10.1016\/S0140-6736(06)68651-0","article-title":"Effect of B vitamins and genetics on success of in-vitro fertilisation: prospective cohort study","volume":"367","author":"Haggarty","year":"2006","journal-title":"Lancet (London, England)"},{"key":"ref21","doi-asserted-by":"publisher","first-page":"450","DOI":"10.1093\/humrep\/del396","article-title":"Methylenetetrahydrofolate reductase C677T and A1298C variants do not affect ongoing pregnancy rates following IVF","volume":"22","author":"Dobson","year":"2007","journal-title":"Hum Reprod"},{"key":"ref22","doi-asserted-by":"publisher","first-page":"52","DOI":"10.1016\/j.rbmo.2021.04.009","article-title":"Association of homocysteine with IVF\/ICSI outcomes stratified by MTHFR C677T polymorphisms: a prospective cohort study","volume":"43","author":"Chen","year":"2021","journal-title":"Reprod Biomed Online"},{"key":"ref23","doi-asserted-by":"publisher","first-page":"1646","DOI":"10.1111\/j.1538-7836.2005.01364.x","article-title":"Mechanisms of homocysteine-induced atherothrombosis","volume":"3","author":"Lentz","year":"2005","journal-title":"J Thrombosis Haemostasis"},{"key":"ref24","doi-asserted-by":"publisher","first-page":"409","DOI":"10.1161\/01.RES.84.4.409","article-title":"Homocysteine enhances neutrophil-endothelial interactions in both cultured human cells and rats in vivo","volume":"84","author":"Dudman","year":"1999","journal-title":"Circ Res"},{"key":"ref25","doi-asserted-by":"publisher","first-page":"2673","DOI":"10.1056\/NEJMoa032845","article-title":"Folate therapy and in-stent restenosis after coronary stenting","volume":"350","author":"Lange","year":"2004","journal-title":"N Engl J Med"},{"key":"ref26","doi-asserted-by":"publisher","first-page":"1879","DOI":"10.3390\/nu15081879","article-title":"Folate supplementation in women with pre-existing diabetes","volume":"15","author":"Perera","year":"2023","journal-title":"Nutrients"},{"key":"ref27","doi-asserted-by":"publisher","first-page":"2715","DOI":"10.3390\/nu14132715","article-title":"Women taking a folic acid supplement in countries with mandatory food fortification programs may be exceeding the upper tolerable limit of folic acid: a systematic review","volume":"14","author":"Ledowsky","year":"2022","journal-title":"Nutrients"},{"key":"ref28","doi-asserted-by":"publisher","first-page":"102566","DOI":"10.1016\/j.jogc.2024.102566","article-title":"Current evidence and controversies related to folate supplementation during pregnancy","volume":"46","author":"Cochrane","year":"2024","journal-title":"J Obstetrics Gynaecol"},{"key":"ref29","doi-asserted-by":"publisher","first-page":"720","DOI":"10.1016\/j.mayocp.2013.05.011","article-title":"Vitamin D for health: a global perspective","volume":"88","author":"Hossein-nezhad","year":"2013","journal-title":"Mayo Clin Proc"},{"key":"ref30","doi-asserted-by":"publisher","first-page":"153","DOI":"10.1007\/s11154-017-9424-1","article-title":"The vitamin D deficiency pandemic: approaches for diagnosis, treatment and prevention","volume":"18","author":"Holick","year":"2017","journal-title":"Rev Endocr Metab Disord"},{"key":"ref31","doi-asserted-by":"publisher","first-page":"f1169","DOI":"10.1136\/bmj.f1169","article-title":"Association between maternal serum 25-hydroxyvitamin D level and pregnancy and neonatal outcomes: systematic review and meta-analysis of observational studies","volume":"346","author":"Aghajafari","year":"2013","journal-title":"BMJ"},{"key":"ref32","doi-asserted-by":"publisher","first-page":"3165","DOI":"10.1210\/jc.2013-1257","article-title":"Maternal vitamin D status and risk of pre-eclampsia: a systematic review and meta-analysis","volume":"98","author":"Tabesh","year":"2013","journal-title":"J Clin Endocrinol Metab"},{"key":"ref33","doi-asserted-by":"publisher","first-page":"111","DOI":"10.1016\/j.fertnstert.2022.04.017","article-title":"Vitamin D and miscarriage: a systematic review and meta-analysis","volume":"118","author":"Tamblyn","year":"2022","journal-title":"Fertil Steril"},{"key":"ref34","doi-asserted-by":"publisher","first-page":"2685","DOI":"10.1093\/humrep\/deae241","article-title":"Nonlinear correlation between serum vitamin D levels and the incidence of endometrial polyps in infertile women","volume":"39","author":"Zhou","year":"2024","journal-title":"Hum Reprod"},{"key":"ref35","doi-asserted-by":"publisher","first-page":"E754","DOI":"10.1210\/jc.2010-2131","article-title":"1,25-Dihydroxyvitamin D3 reduces TGF-beta3-induced fibrosis-related gene expression in human uterine leiomyoma cells","volume":"96","author":"Halder","year":"2011","journal-title":"J Clin Endocrinol Metab"},{"key":"ref36","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1111\/j.1600-0625.2010.01202.x","article-title":"Vitamin D: an ancient hormone","volume":"20","author":"Bikle","year":"2011","journal-title":"Exp Dermatol"},{"key":"ref37","doi-asserted-by":"publisher","first-page":"229","DOI":"10.2174\/156800906776842939","article-title":"Vitamin D receptor is a novel drug target for ovarian cancer treatment","volume":"6","author":"Zhang","year":"2006","journal-title":"Curr Cancer Drug Targets"},{"key":"ref38","doi-asserted-by":"publisher","first-page":"266","DOI":"10.1056\/NEJMra070553","article-title":"Vitamin D deficiency","volume":"357","author":"Holick","year":"2007","journal-title":"N Engl J Med"},{"key":"ref39","doi-asserted-by":"publisher","first-page":"1770","DOI":"10.1126\/science.1123933","article-title":"Toll-like receptor triggering of a vitamin D-mediated human antimicrobial response","volume":"311","author":"Liu","year":"2006","journal-title":"Science (New York, NY)"},{"key":"ref40","doi-asserted-by":"publisher","first-page":"357","DOI":"10.1016\/S0083-6729(02)64010-5","article-title":"Antiproliferative action of vitamin D","volume":"64","author":"Ylikomi","year":"2002","journal-title":"Vitam Horm"},{"key":"ref41","doi-asserted-by":"publisher","first-page":"605","DOI":"10.1007\/s00223-020-00795-z","article-title":"Gestational folate and offspring bone health; the vitamin D in pregnancy study","volume":"108","author":"Percival","year":"2021","journal-title":"Calcif Tissue Int"},{"key":"ref42","doi-asserted-by":"publisher","first-page":"234","DOI":"10.1016\/j.jbspin.2008.11.002","article-title":"Bone tissue and hyperhomocysteinemia","volume":"76","author":"Levasseur","year":"2009","journal-title":"Joint Bone Spine"},{"key":"ref43","doi-asserted-by":"publisher","first-page":"132","DOI":"10.3390\/nu15010132","article-title":"Vitamin D, folic acid and vitamin B(12) can reverse vitamin D deficiency-induced learning and memory impairment by altering 27-hydroxycholesterol and S-adenosylmethionine","volume":"15","author":"Wang","year":"2022","journal-title":"Nutrients"},{"key":"ref44","doi-asserted-by":"publisher","first-page":"633","DOI":"10.1210\/jc.2013-3262","article-title":"The relationship between 25-hydroxyvitamin D and homocysteine in asymptomatic adults","volume":"99","author":"Amer","year":"2014","journal-title":"J Clin Endocrinol Metab"},{"key":"ref45","doi-asserted-by":"publisher","first-page":"1276","DOI":"10.1093\/humrep\/deaa095","article-title":"Effects of MTHFR C677T polymorphism on vitamin D, homocysteine and natural killer cell cytotoxicity in women with recurrent pregnancy losses","volume":"35","author":"Ota","year":"2020","journal-title":"Hum Reprod"},{"key":"ref46","article-title":"The National Academies Collection: Reports funded by National Institutes of Health","volume-title":"Dietary reference intakes for calcium and vitamin D","author":"Ross","year":"2011"},{"key":"ref47","doi-asserted-by":"publisher","first-page":"1911","DOI":"10.1210\/jc.2011-0385","article-title":"Evaluation, treatment, and prevention of vitamin D deficiency: an Endocrine Society clinical practice guideline","volume":"96","author":"Holick","year":"2011","journal-title":"J Clin Endocrinol Metab"},{"key":"ref48","first-page":"1","article-title":"Prevention and management of osteoporosis. World Health Organization technical report series","year":"2003"},{"key":"ref49","doi-asserted-by":"publisher","first-page":"1173","DOI":"10.1037\/0022-3514.51.6.1173","article-title":"The moderator-mediator variable distinction in social psychological research: conceptual, strategic, and statistical considerations","volume":"51","author":"Baron","year":"1986","journal-title":"J Pers Soc Psychol"},{"key":"ref50","doi-asserted-by":"publisher","first-page":"121","DOI":"10.1006\/mgme.2000.3027","article-title":"Folic acid: nutritional biochemistry, molecular biology, and role in disease processes","volume":"71","author":"Lucock","year":"2000","journal-title":"Mol Genet Metab"},{"key":"ref51","doi-asserted-by":"publisher","first-page":"766","DOI":"10.1016\/j.rbmo.2014.01.017","article-title":"Folic acid supplementation and IVF pregnancy outcome in women with unexplained infertility","volume":"28","author":"Murto","year":"2014","journal-title":"Reprod Biomed Online"},{"key":"ref52","doi-asserted-by":"publisher","first-page":"k3478","DOI":"10.1136\/bmj.k3478","article-title":"Effect of high dose folic acid supplementation in pregnancy on pre-eclampsia (FACT): double blind, phase III, randomised controlled, international, multicentre trial","volume":"362","author":"Wen","year":"2018","journal-title":"BMJ (Clinical research ed)"},{"key":"ref53","doi-asserted-by":"publisher","first-page":"723","DOI":"10.1359\/jbmr.2003.18.4.723","article-title":"A common methylenetetrahydrofolate reductase (C677T) polymorphism is associated with low bone mineral density and increased fracture incidence after menopause: longitudinal data from the Danish osteoporosis prevention study","volume":"18","author":"Abrahamsen","year":"2003","journal-title":"J Bone Miner Res"},{"key":"ref54","first-page":"215","article-title":"MTHFR c.677C>T polymorphism as an independent predictor of peak bone mass in Danish men--results from the Odense androgen study","volume-title":"Bone","author":"Abrahamsen","year":"2006"},{"key":"ref55","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1161\/01.CIR.93.1.7","article-title":"Relation between folate status, a common mutation in methylenetetrahydrofolate reductase, and plasma homocysteine concentrations","volume":"93","author":"Jacques","year":"1996","journal-title":"Circulation"},{"key":"ref56","doi-asserted-by":"publisher","first-page":"169","DOI":"10.1006\/mgme.1998.2714","article-title":"A second genetic polymorphism in methylenetetrahydrofolate reductase (MTHFR) associated with decreased enzyme activity","volume":"64","author":"Weisberg","year":"1998","journal-title":"Mol Genet Metab"},{"key":"ref57","doi-asserted-by":"publisher","first-page":"409","DOI":"10.1016\/S0021-9150(00)00671-7","article-title":"The 1298A\u2192C polymorphism in methylenetetrahydrofolate reductase (MTHFR): in vitro expression and association with homocysteine","volume":"156","author":"Weisberg","year":"2001","journal-title":"Atherosclerosis"},{"key":"ref58","doi-asserted-by":"publisher","first-page":"954","DOI":"10.1093\/humrep\/15.4.954","article-title":"Maternal homocysteine and chorionic vascularization in recurrent early pregnancy loss","volume":"15","author":"Nelen","year":"2000","journal-title":"Hum Reprod"},{"key":"ref59","doi-asserted-by":"publisher","first-page":"e23166","DOI":"10.1002\/ajhb.23166","article-title":"Vitamin D and folate: a reciprocal environmental association based on seasonality and genetic disposition","volume":"30","author":"Lucock","year":"2018","journal-title":"Am J Hum Biol"},{"key":"ref60","doi-asserted-by":"publisher","first-page":"1048","DOI":"10.3390\/foods13071048","article-title":"High dietary folic acid supplementation reduced the composition of fatty acids and amino acids in fortified eggs","volume":"13","author":"Yu","year":"2024","journal-title":"Foods (Basel, Switzerland)"},{"key":"ref61","doi-asserted-by":"publisher","first-page":"2991","DOI":"10.1002\/jbmr.493","article-title":"1,25-dihydroxyvitamin D3 influences cellular homocysteine levels in murine preosteoblastic MC3T3-E1 cells by direct regulation of cystathionine \u03b2-synthase","volume":"26","author":"Kriebitzsch","year":"2011","journal-title":"J Bone Mineral Res"},{"key":"ref62","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1016\/j.nutres.2018.07.012","article-title":"Vitamin D(3) prevents cardiovascular diseases by lowering serum total homocysteine concentrations in overweight reproductive women: a randomized, placebo-controlled clinical trial","volume":"59","author":"Al-Bayyari","year":"2018","journal-title":"Nutr Res"},{"key":"ref63","doi-asserted-by":"publisher","first-page":"676","DOI":"10.1161\/01.HYP.0000182662.82666.37","article-title":"Vitamin D intake and risk of incident hypertension: results from three large prospective cohort studies","volume":"46","author":"Forman","year":"2005","journal-title":"Hypertension"},{"key":"ref64","doi-asserted-by":"publisher","first-page":"846","DOI":"10.1161\/CIRCULATIONAHA.106.673491","article-title":"Calcium\/vitamin D supplementation and cardiovascular events","volume":"115","author":"Hsia","year":"2007","journal-title":"Circulation"}],"container-title":["Frontiers in Nutrition"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnut.2025.1644302\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,9,11]],"date-time":"2025-09-11T04:13:01Z","timestamp":1757563981000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnut.2025.1644302\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9,11]]},"references-count":64,"alternative-id":["10.3389\/fnut.2025.1644302"],"URL":"https:\/\/doi.org\/10.3389\/fnut.2025.1644302","relation":{},"ISSN":["2296-861X"],"issn-type":[{"value":"2296-861X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,9,11]]},"article-number":"1644302"}}