{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T12:46:38Z","timestamp":1787921198288,"version":"build-2784847793"},"reference-count":50,"publisher":"Public Library of Science (PLoS)","issue":"3","license":[{"start":{"date-parts":[[2023,3,16]],"date-time":"2023-03-16T00:00:00Z","timestamp":1678924800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:sec id=\"sec001\"><jats:title>Introduction<\/jats:title><jats:p>Bone mineral density (BMD) in adolescence is a crucial determinant in osteoporosis and fragility fractures in older age. Vitamin E is the most abundant lipid-soluble antioxidant present in the blood. However, the association of vitamin E status with BMD in children and adolescents remains unclear.<\/jats:p><\/jats:sec><jats:sec id=\"sec002\"><jats:title>Methods<\/jats:title><jats:p>We first measured the association of vitamin E status (serum \u03b1- and \u03b3 tocopherol) with BMD in children and adolescents with the National Health and Nutrition Examination Survey (NHANES). Multiple linear regression models were performed to evaluate their relationship after adjusting for a large range of covariates. Stratified analyses and interaction tests were used to explore their effects on different genders, ages, and races\/ethnicities.<\/jats:p><\/jats:sec><jats:sec id=\"sec003\"><jats:title>Results<\/jats:title><jats:p>13,606 children and adolescents from NHANES (2005\u20132006, 2017\u20132018) were included in our analysis. Compared with the lowest \u03b1-tocopherol quartile, individuals in the highest \u03b1-tocopherol quartile are likelier to be Non-Hispanic White and have a higher value of poverty income ratio (PIR). They have a lower value of serum phosphorus and lumbar spine BMD. Every 1umol\/L increase in serum \u03b1- and \u03b3- tocopherol, the lumbar spine BMD decreased by -0.0016 and -0.0068 g\/cm<jats:sup>2<\/jats:sup>. Compared with the lowest quartile serum \u03b1- and \u03b3- tocopherol concentration, individuals in the highest quartile have a -0.0223 and -0.0329 g\/cm<jats:sup>2<\/jats:sup>lower mean BMD, respectively. Interaction effects suggest that the negative effect is more prominent among female youth, individuals aged 8\u201313 years, non-Hispanic whites, Mexican Americans, and non-Hispanic blacks.<\/jats:p><\/jats:sec><jats:sec id=\"sec004\"><jats:title>Conclusions<\/jats:title><jats:p>Our study indicates serum \u03b1- and \u03b3-tocopherol are negatively correlated with lumbar BMD. Age, gender, and race may have a modifying effect on this relationship. Our study has an important clinical implication. A higher vitamin E status for children and adolescents could not improve BMD, even decrease BMD. More prospective research with stronger evidence is needed to verify our findings and their underlying mechanisms.<\/jats:p><\/jats:sec>","DOI":"10.1371\/journal.pone.0283127","type":"journal-article","created":{"date-parts":[[2023,3,16]],"date-time":"2023-03-16T17:45:07Z","timestamp":1678988707000},"page":"e0283127","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":11,"title":["Associations between vitamin E status and bone mineral density in children and adolescents aged 8\u201319 years: Evidence based on NHANES 2005\u20132006, 2017\u20132018"],"prefix":"10.1371","volume":"18","author":[{"given":"Aiyong","family":"Cui","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7256-6279","authenticated-orcid":true,"given":"Peilun","family":"Xiao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiqiang","family":"Fan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuan","family":"Zeng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hu","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Zhuang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2023,3,16]]},"reference":[{"key":"pone.0283127.ref001","doi-asserted-by":"crossref","first-page":"10129","DOI":"10.1038\/ncomms10129","article-title":"Sequence variants in the PTCH1 gene associate with spine bone mineral density and osteoporotic fractures","volume":"7","author":"U Styrkarsdottir","year":"2016","journal-title":"Nat Commun"},{"key":"pone.0283127.ref002","article-title":"Global, regional prevalence, and risk factors of osteoporosis according to the World Health Organization diagnostic criteria: a systematic review and meta-analysis.","author":"PL Xiao","year":"2022","journal-title":"Osteoporos Int"},{"key":"pone.0283127.ref003","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1007\/s11657-013-0136-1","article-title":"Osteoporosis in the European Union: medical management, epidemiology and economic burden. A report prepared in collaboration with the International Osteoporosis Foundation (IOF) and the European Federation of Pharmaceutical Industry Associations (EFPIA)","volume":"8","author":"E Hernlund","year":"2013","journal-title":"Arch Osteoporos"},{"key":"pone.0283127.ref004","doi-asserted-by":"crossref","first-page":"799","DOI":"10.1172\/JCI117034","article-title":"Timing of peak bone mass in Caucasian females and its implication for the prevention of osteoporosis. Inference from a cross-sectional model","volume":"93","author":"V Matkovic","year":"1994","journal-title":"J Clin Invest"},{"key":"pone.0283127.ref005","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1016\/j.maturitas.2020.05.004","article-title":"How to manage osteoporosis before the age of 50.","volume":"138","author":"S Rozenberg","year":"2020","journal-title":"Maturitas"},{"key":"pone.0283127.ref006","doi-asserted-by":"crossref","first-page":"877","DOI":"10.1136\/bjsports-2011-090188","article-title":"Physical activity in childhood and bone health","volume":"45","author":"CA Boreham","year":"2011","journal-title":"Br J Sports Med"},{"key":"pone.0283127.ref007","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1007\/s11914-020-00588-1","article-title":"Exercise and Peak Bone Mass","volume":"18","author":"MK Karlsson","year":"2020","journal-title":"Curr Osteoporos Rep"},{"key":"pone.0283127.ref008","doi-asserted-by":"crossref","first-page":"928752","DOI":"10.3389\/fendo.2022.928752","article-title":"Blood Lead Level Is Negatively Associated With Bone Mineral Density in U.S. Children and Adolescents Aged 8\u201319 Years.","volume":"13","author":"A Cui","year":"2022","journal-title":"Front Endocrinol (Lausanne)"},{"key":"pone.0283127.ref009","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1016\/j.bone.2009.03.657","article-title":"Early diet and peak bone mass: 20 year follow-up of a randomized trial of early diet in infants born preterm","volume":"45","author":"MS Fewtrell","year":"2009","journal-title":"Bone"},{"key":"pone.0283127.ref010","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1016\/j.freeradbiomed.2021.10.029","article-title":"Vitamin E research: Past, now and future","volume":"177","author":"R. Brigelius-Floh\u00e9","year":"2021","journal-title":"Free Radic Biol Med"},{"key":"pone.0283127.ref011","doi-asserted-by":"crossref","first-page":"714","DOI":"10.1093\/ajcn\/74.6.714","article-title":"gamma-tocopherol, the major form of vitamin E in the US diet, deserves more attention","volume":"74","author":"Q Jiang","year":"2001","journal-title":"Am J Clin Nutr"},{"key":"pone.0283127.ref012","doi-asserted-by":"crossref","first-page":"588","DOI":"10.1002\/mnfr.200900457","article-title":"Analysis of vitamin E metabolites in biological specimen","volume":"54","author":"M. Birringer","year":"2010","journal-title":"Mol Nutr Food Res"},{"key":"pone.0283127.ref013","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1186\/s12916-022-02366-5","article-title":"Association between circulating vitamin E and ten common cancers: evidence from large-scale Mendelian randomization analysis and a longitudinal cohort study.","volume":"20","author":"J Xin","year":"2022","journal-title":"BMC Med"},{"key":"pone.0283127.ref014","doi-asserted-by":"crossref","first-page":"955878","DOI":"10.3389\/fnagi.2022.955878","article-title":"Association of vitamin E intake in diet and supplements with risk of dementia: A meta-analysis.","volume":"14","author":"R Zhao","year":"2022","journal-title":"Front Aging Neurosci"},{"key":"pone.0283127.ref015","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1056\/NEJM200001203420302","article-title":"Vitamin E supplementation and cardiovascular events in high-risk patients","volume":"342","author":"S Yusuf","year":"2000","journal-title":"N Engl J Med"},{"key":"pone.0283127.ref016","doi-asserted-by":"crossref","first-page":"699","DOI":"10.1038\/sj.ki.5001651","article-title":"Vitamin E attenuates crystal formation in rat kidneys: roles of renal tubular cell death and crystallization inhibitors","volume":"70","author":"HS Huang","year":"2006","journal-title":"Kidney Int"},{"key":"pone.0283127.ref017","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1007\/s00223-008-9190-x","article-title":"Beneficial effects of tocotrienol and tocopherol on bone histomorphometric parameters in sprague-dawley male rats after nicotine cessation","volume":"84","author":"H Hermizi","year":"2009","journal-title":"Calcif Tissue Int"},{"key":"pone.0283127.ref018","first-page":"623","article-title":"Vitamin E deficiency reduced lumbar bone calcium content in female rats","volume":"59","author":"M Norazlina","year":"2004","journal-title":"Med J Malaysia"},{"key":"pone.0283127.ref019","doi-asserted-by":"crossref","first-page":"589","DOI":"10.1038\/nm.2659","article-title":"Vitamin E decreases bone mass by stimulating osteoclast fusion","volume":"18","author":"K Fujita","year":"2012","journal-title":"Nat Med"},{"key":"pone.0283127.ref020","doi-asserted-by":"crossref","first-page":"1245","DOI":"10.1007\/s00198-016-3855-5","article-title":"Associations between serum vitamin E concentration and bone mineral density in the US elderly population","volume":"28","author":"J Zhang","year":"2017","journal-title":"Osteoporos Int"},{"key":"pone.0283127.ref021","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1017\/S0007114515004134","article-title":"Association of dietary and serum vitamin E with bone mineral density in middle-aged and elderly Chinese adults: a cross-sectional study","volume":"115","author":"WQ Shi","year":"2016","journal-title":"Br J Nutr"},{"key":"pone.0283127.ref022","doi-asserted-by":"crossref","first-page":"2281","DOI":"10.1007\/s00198-015-3470-x","article-title":"Vitamin E homologues \u03b1- and \u03b3-tocopherol are not associated with bone turnover markers or bone mineral density in peri-menopausal and post-menopausal women","volume":"27","author":"TC Yang","year":"2016","journal-title":"Osteoporos Int"},{"key":"pone.0283127.ref023","doi-asserted-by":"crossref","first-page":"576","DOI":"10.1016\/j.bone.2005.09.021","article-title":"Physical activity and strength of the femoral neck during the adolescent growth spurt: a longitudinal analysis","volume":"38","author":"MR Forwood","year":"2006","journal-title":"Bone"},{"key":"pone.0283127.ref024","doi-asserted-by":"crossref","first-page":"1153s","DOI":"10.1093\/jn\/126.suppl_4.1153S","article-title":"Calcium, phosphorus and human bone development","volume":"126","author":"JJ Anderson","year":"1996","journal-title":"J Nutr"},{"key":"pone.0283127.ref025","first-page":"14","article-title":"The Association between Lead Exposure and Bone Mineral Density in Childhood and Adolescence: Results from NHANES 1999\u20132006 and 2011\u20132018.","author":"T Li","year":"2022","journal-title":"Nutrients"},{"key":"pone.0283127.ref026","doi-asserted-by":"crossref","first-page":"1533","DOI":"10.2174\/13894501113149990178","article-title":"A review of the possible mechanisms of action of tocotrienol\u2014a potential antiosteoporotic agent.","volume":"14","author":"KY Chin","year":"2013","journal-title":"Curr Drug Targets"},{"key":"pone.0283127.ref027","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1186\/1746-160X-8-25","article-title":"An in vitro study of osteoblast vitality influenced by the vitamins C and E.","volume":"8","author":"K Urban","year":"2012","journal-title":"Head Face Med"},{"key":"pone.0283127.ref028","doi-asserted-by":"crossref","first-page":"951","DOI":"10.1292\/jvms.09-0487","article-title":"Effects of vitamin E on the osteoblast differentiation","volume":"72","author":"S Soeta","year":"2010","journal-title":"J Vet Med Sci"},{"key":"pone.0283127.ref029","author":"KH Ahn","year":"2011","journal-title":"Microarray Analysis of Gene Expression During Differentiation of Human Mesenchymal Stem Cells Treated with Vitamin E in vitro into Osteoblasts."},{"key":"pone.0283127.ref030","doi-asserted-by":"crossref","first-page":"825985","DOI":"10.1155\/2013\/825985","article-title":"Effects of vitamin e on bone biomechanical and histomorphometric parameters in ovariectomized rats","volume":"2013","author":"RG Feresin","year":"2013","journal-title":"J Osteoporos"},{"key":"pone.0283127.ref031","doi-asserted-by":"crossref","first-page":"161527","DOI":"10.1155\/2012\/161527","article-title":"Two different isomers of vitamin e prevent bone loss in postmenopausal osteoporosis rat model","volume":"2012","author":"N Muhammad","year":"2012","journal-title":"Evid Based Complement Alternat Med"},{"key":"pone.0283127.ref032","doi-asserted-by":"crossref","first-page":"505","DOI":"10.5114\/aoms.2010.14460","article-title":"Vitamin E reversed nicotine-induced toxic effects on bone biochemical markers in male rats","volume":"6","author":"M Norazlina","year":"2010","journal-title":"Arch Med Sci"},{"key":"pone.0283127.ref033","doi-asserted-by":"crossref","first-page":"1209","DOI":"10.1016\/j.freeradbiomed.2013.09.004","article-title":"Evaluation of long-term vitamin E insufficiency or excess on bone mass, density, and microarchitecture in rodents","volume":"65","author":"UT Iwaniec","year":"2013","journal-title":"Free Radic Biol Med"},{"key":"pone.0283127.ref034","doi-asserted-by":"crossref","first-page":"272","DOI":"10.1007\/s00223-004-0269-8","article-title":"Vitamin E provides protection for bone in mature hindlimb unloaded male rats","volume":"76","author":"BJ Smith","year":"2005","journal-title":"Calcif Tissue Int"},{"key":"pone.0283127.ref035","doi-asserted-by":"crossref","first-page":"370","DOI":"10.1016\/j.maturitas.2010.06.003","article-title":"A review of select vitamins and minerals used by postmenopausal women.","volume":"66","author":"C Dennehy","year":"2010","journal-title":"Maturitas"},{"key":"pone.0283127.ref036","doi-asserted-by":"crossref","first-page":"581","DOI":"10.1093\/ajcn\/82.3.581","article-title":"Lack of a relation between vitamin and mineral antioxidants and bone mineral density: results from the Women\u2019s Health Initiative","volume":"82","author":"RL Wolf","year":"2005","journal-title":"Am J Clin Nutr"},{"key":"pone.0283127.ref037","first-page":"13","article-title":"Circulating Alpha-Tocopherol Levels, Bone Mineral Density, and Fracture: Mendelian Randomization Study.","author":"K Micha\u00eblsson","year":"2021","journal-title":"Nutrients"},{"key":"pone.0283127.ref038","doi-asserted-by":"crossref","first-page":"107","DOI":"10.3945\/ajcn.113.064691","article-title":"Intake and serum concentrations of \u03b1-tocopherol in relation to fractures in elderly women and men: 2 cohort studies","volume":"99","author":"K Micha\u00eblsson","year":"2014","journal-title":"Am J Clin Nutr"},{"key":"pone.0283127.ref039","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1186\/s12891-021-03997-0","article-title":"Associations of serum vitamins levels with bone mineral density in the different race-ethnicities US adults","volume":"22","author":"X Li","year":"2021","journal-title":"BMC Musculoskelet Disord"},{"key":"pone.0283127.ref040","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1093\/ajcn\/79.1.155","article-title":"Nutritional associations with bone loss during the menopausal transition: evidence of a beneficial effect of calcium, alcohol, and fruit and vegetable nutrients and of a detrimental effect of fatty acids","volume":"79","author":"HM Macdonald","year":"2004","journal-title":"Am J Clin Nutr"},{"key":"pone.0283127.ref041","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1007\/s00774-013-0432-2","article-title":"Lower vitamin E serum levels are associated with osteoporosis in early postmenopausal women: a cross-sectional study","volume":"31","author":"JM Mata-Granados","year":"2013","journal-title":"J Bone Miner Metab"},{"key":"pone.0283127.ref042","doi-asserted-by":"crossref","first-page":"1368","DOI":"10.1002\/jbmr.1566","article-title":"Effects of vitamin E on bone turnover markers among US postmenopausal women","volume":"27","author":"MS Hamidi","year":"2012","journal-title":"J Bone Miner Res"},{"key":"pone.0283127.ref043","doi-asserted-by":"crossref","first-page":"647","DOI":"10.1016\/S0002-8223(21)05428-6","article-title":"Vitamin E content of foods.","volume":"75","author":"PJ McLaughlin","year":"1979","journal-title":"J Am Diet Assoc"},{"key":"pone.0283127.ref044","doi-asserted-by":"crossref","first-page":"4395","DOI":"10.4049\/jimmunol.0803659","article-title":"Isoforms of vitamin E have opposing immunoregulatory functions during inflammation by regulating leukocyte recruitment","volume":"182","author":"S Berdnikovs","year":"2009","journal-title":"J Immunol"},{"key":"pone.0283127.ref045","doi-asserted-by":"crossref","first-page":"1451","DOI":"10.1002\/jbmr.5650090918","article-title":"Bone mineral density of total body, spine, and femoral neck in children and young adults: a cross-sectional and longitudinal study","volume":"9","author":"PW Lu","year":"1994","journal-title":"J Bone Miner Res"},{"key":"pone.0283127.ref046","doi-asserted-by":"crossref","first-page":"503","DOI":"10.3945\/an.114.006254","article-title":"Vitamin E inadequacy in humans: causes and consequences.","volume":"5","author":"MG Traber","year":"2014","journal-title":"Adv Nutr"},{"key":"pone.0283127.ref047","doi-asserted-by":"crossref","first-page":"1349","DOI":"10.1016\/j.jaci.2020.04.019","article-title":"Associations of \u03b1- and \u03b3-tocopherol during early life with lung function in childhood","volume":"146","author":"R Kumar","year":"2020","journal-title":"J Allergy Clin Immunol"},{"key":"pone.0283127.ref048","article-title":"Supplementary vitamin E, selenium, cysteine and riboflavin for preventing kwashiorkor in preschool children in developing countries.","volume":"2010","author":"CC Odigwe","year":"2010","journal-title":"Cochrane Database Syst Rev"},{"key":"pone.0283127.ref049","doi-asserted-by":"crossref","first-page":"1553","DOI":"10.1111\/j.1365-2036.2006.03161.x","article-title":"Effect of vitamin E on aminotransferase levels and insulin resistance in children with non-alcoholic fatty liver disease","volume":"24","author":"V Nobili","year":"2006","journal-title":"Aliment Pharmacol Ther"},{"key":"pone.0283127.ref050","first-page":"81","article-title":"Laboratory medicine best practice guideline: vitamins a, e and the carotenoids in blood","volume":"35","author":"RF Greaves","year":"2014","journal-title":"Clin Biochem Rev"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0283127","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,12,9]],"date-time":"2023-12-09T02:33:53Z","timestamp":1702089233000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0283127"}},"subtitle":[],"editor":[{"given":"Hiroshi","family":"Kaji","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2023,3,16]]},"references-count":50,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2023,3,16]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0283127","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,3,16]]}}}