{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T03:53:06Z","timestamp":1784692386526,"version":"3.55.0"},"reference-count":36,"publisher":"BMJ","issue":"6","license":[{"start":{"date-parts":[[2021,6,16]],"date-time":"2021-06-16T00:00:00Z","timestamp":1623801600000},"content-version":"unspecified","delay-in-days":15,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100007957","name":"Chongqing Municipal Education Commission","doi-asserted-by":"publisher","award":["CYS19199"],"award-info":[{"award-number":["CYS19199"]}],"id":[{"id":"10.13039\/501100007957","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["BMJ Open"],"accepted":{"date-parts":[[2021,5,27]]},"published-print":{"date-parts":[[2021,6]]},"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Approximately 7.2% of children in the world suffer from attention-deficit\/hyperactivity disorder (ADHD). Due to the availability of the osmotic-release oral-system methylphenidate, ADHD currently has a remission rate of up to 30.72%. Nevertheless, it has been reported that patients with ADHD tend to exhibit vitamin A and vitamin D deficiency, which may aggravate the symptoms of ADHD. This study aims to determine the effect of vitamin A and vitamin D supplementation as adjunctive therapy to methylphenidate on the symptoms of ADHD.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and analysis<\/jats:title>\n                    <jats:p>This is a parallel, prospective, interventional multicentric study. Patients will be enrolled from the southern, central and northern parts of China. A target of 504 patients will be followed for 8 weeks. They will be allocated into three groups (vitamin AD, vitamin D and placebo) and administered the interventions accordingly. Data on changes in the symptoms of ADHD as well as changes in the serum concentrations of vitamin A and vitamin D will be recorded. Both responders and nonresponders based on the sociodemographic and clinical data will also be described to mitigate selection bias.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Ethics and dissemination<\/jats:title>\n                    <jats:p>This study is performed in accordance with the Declaration of Helsinki and was approved by the Institutional Review Board of Children\u2019s Hospital of Chongqing Medical University, China (approval number: (2019) IRB (STUDY) number 262). The results of the trial will be reported in peer-reviewed scientific journals and academic conferences regardless of the outcomes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial registration number<\/jats:title>\n                    <jats:p>\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"clintrialgov\" xlink:href=\"NCT04284059\">NCT04284059<\/jats:ext-link>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/bmjopen-2021-050541","type":"journal-article","created":{"date-parts":[[2021,6,16]],"date-time":"2021-06-16T13:02:43Z","timestamp":1623848563000},"page":"e050541","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":11,"title":["Adjuvant effects of vitamin A and vitamin D supplementation on treatment of children with attention-deficit\/hyperactivity disorder: a study protocol for a randomised, double-blinded, placebo-controlled, multicentric trial in China"],"prefix":"10.1136","volume":"11","clinical-trial-number":[{"clinical-trial-number":"nct04284059","registry":"10.18810\/clinical-trials-gov"}],"author":[{"given":"Ping","family":"Zhou","sequence":"first","affiliation":[{"name":"Division of Growth, Development and Mental health of Children and Adolescence, Children\u2019s Hospital of Chongqing Medical University, Chongqing, People\u2019s Republic of China"},{"name":"Chongqing Key Laboratory of Child Health and Nutrition, Ministry of Education Key Laboratory of Child Development and Disorder, China International Science and Technology Cooperation Base of Child Development and Critical Disorders, National Clinical Research Center for Child Health and Disorders (Chongqing), Chongqing, People\u2019s Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark Lee","family":"Wolraich","sequence":"additional","affiliation":[{"name":"Section of Developmental and Behavioral Pediatrics, University of Oklahoma, Oklahoma City, Oklahoma, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ai-hua","family":"Cao","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Qilu Hospital of Shandong University, Brain Science Research Institute of Shandong University, Jinan, People\u2019s Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fei-Yong","family":"Jia","sequence":"additional","affiliation":[{"name":"Department of Developmental and Behavioral Pediatrics, The First Hospital of Jilin University, Changchun, People\u2019s Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bin","family":"Liu","sequence":"additional","affiliation":[{"name":"Clinical Pharmacy Research, Children\u2019s Hospital of Chongqing Medical University, Chongqing, People\u2019s Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Zhu","sequence":"additional","affiliation":[{"name":"Division of Growth, Development and Mental health of Children and Adolescence, Children\u2019s Hospital of Chongqing Medical University, Chongqing, People\u2019s Republic of China"},{"name":"Chongqing Key Laboratory of Child Health and Nutrition, Ministry of Education Key Laboratory of Child Development and Disorder, China International Science and Technology Cooperation Base of Child Development and Critical Disorders, National Clinical Research Center for Child Health and Disorders (Chongqing), Chongqing, People\u2019s Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongfang","family":"Liu","sequence":"additional","affiliation":[{"name":"Division of Clinical Nutrition, Children\u2019s Hospital of Chongqing Medical University, Chongqing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoli","family":"Li","sequence":"additional","affiliation":[{"name":"Division of Growth, Development and Mental health of Children and Adolescence, Children\u2019s Hospital of Chongqing Medical University, Chongqing, People\u2019s Republic of China"},{"name":"Chongqing Key Laboratory of Child Health and Nutrition, Ministry of Education Key Laboratory of Child Development and Disorder, China International Science and Technology Cooperation Base of Child Development and Critical Disorders, National Clinical Research Center for Child Health and Disorders (Chongqing), Chongqing, People\u2019s Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2596-3754","authenticated-orcid":false,"given":"Chao","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Child Care, The First People\u2019s Hospital of Chongqing Liangjiang New Area, Chongqing, People\u2019s Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bin","family":"Peng","sequence":"additional","affiliation":[{"name":"School of Public Health and Management, Department of Health Statistics, Chongqing Medical University, Chongqing, People\u2019s Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ting","family":"Yang","sequence":"additional","affiliation":[{"name":"Chongqing Key Laboratory of Child Health and Nutrition, Ministry of Education Key Laboratory of Child Development and Disorder, China International Science and Technology Cooperation Base of Child Development and Critical Disorders, National Clinical Research Center for Child Health and Disorders (Chongqing), Chongqing, People\u2019s Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Chen","sequence":"additional","affiliation":[{"name":"Chongqing Key Laboratory of Child Health and Nutrition, Ministry of Education Key Laboratory of Child Development and Disorder, China International Science and Technology Cooperation Base of Child Development and Critical Disorders, National Clinical Research Center for Child Health and Disorders (Chongqing), Chongqing, People\u2019s Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qian","family":"Cheng","sequence":"additional","affiliation":[{"name":"Division of Growth, Development and Mental health of Children and Adolescence, Children\u2019s Hospital of Chongqing Medical University, Chongqing, People\u2019s Republic of China"},{"name":"Chongqing Key Laboratory of Child Health and Nutrition, Ministry of Education Key Laboratory of Child Development and Disorder, China International Science and Technology Cooperation Base of Child Development and Critical Disorders, National Clinical Research Center for Child Health and Disorders (Chongqing), Chongqing, People\u2019s Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tingyu","family":"Li","sequence":"additional","affiliation":[{"name":"Division of Growth, Development and Mental health of Children and Adolescence, Children\u2019s Hospital of Chongqing Medical University, Chongqing, People\u2019s Republic of China"},{"name":"Chongqing Key Laboratory of Child Health and Nutrition, Ministry of Education Key Laboratory of Child Development and Disorder, China International Science and Technology Cooperation Base of Child Development and Critical Disorders, National Clinical Research Center for Child Health and Disorders (Chongqing), Chongqing, People\u2019s Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2614-1528","authenticated-orcid":false,"given":"Li","family":"Chen","sequence":"additional","affiliation":[{"name":"Division of Growth, Development and Mental health of Children and Adolescence, Children\u2019s Hospital of Chongqing Medical University, Chongqing, People\u2019s Republic of China"},{"name":"Chongqing Key Laboratory of Child Health and Nutrition, Ministry of Education Key Laboratory of Child Development and Disorder, China International Science and Technology Cooperation Base of Child Development and Critical Disorders, National Clinical Research Center for Child Health and Disorders (Chongqing), Chongqing, People\u2019s Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2021,6,16]]},"reference":[{"key":"2025121411212004000_11.6.e050541.1","doi-asserted-by":"publisher","DOI":"10.1542\/peds.2019-2528"},{"key":"2025121411212004000_11.6.e050541.2","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1016\/S2215-0366(16)00096-1","article-title":"Moving towards causality in attention-deficit hyperactivity disorder: overview of neural and genetic mechanisms","volume":"3","author":"Gallo","year":"2016","journal-title":"Lancet Psychiatry"},{"key":"2025121411212004000_11.6.e050541.3","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1111\/j.1440-1819.2011.02289.x","article-title":"Naturalistic exploration of the effect of osmotic release oral system-methylphenidate on remission rate and functional improvement in Taiwanese children with attention-deficit-hyperactivity disorder","volume":"66","author":"Tzang","year":"2012","journal-title":"Psychiatry Clin Neurosci"},{"key":"2025121411212004000_11.6.e050541.4","doi-asserted-by":"publisher","DOI":"10.1016\/j.neubiorev.2018.02.001"},{"key":"2025121411212004000_11.6.e050541.5","doi-asserted-by":"publisher","DOI":"10.1093\/advances\/nmx002"},{"key":"2025121411212004000_11.6.e050541.6","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1007\/s12402-018-0276-7","article-title":"Vitamin D levels in children and adolescents with attention-deficit hyperactivity disorder (ADHD): a meta-analysis","volume":"11","author":"Kotsi","year":"2019","journal-title":"Atten Defic Hyperact Disord"},{"key":"2025121411212004000_11.6.e050541.7","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.pnpbp.2018.01.016","article-title":"Genetic variants of the folate metabolic system and mild hyperhomocysteinemia may affect ADHD associated behavioral problems","volume":"84","author":"Saha","year":"2018","journal-title":"Prog Neuropsychopharmacol Biol Psychiatry"},{"key":"2025121411212004000_11.6.e050541.8","doi-asserted-by":"crossref","first-page":"1013","DOI":"10.1001\/jamaneurol.2018.0611","article-title":"Use of vitamins and dietary supplements by patients with multiple sclerosis: a review","volume":"75","author":"Evans","year":"2018","journal-title":"JAMA Neurol"},{"key":"2025121411212004000_11.6.e050541.9","doi-asserted-by":"publisher","DOI":"10.1007\/s40263-014-0148-4"},{"key":"2025121411212004000_11.6.e050541.10","doi-asserted-by":"publisher","DOI":"10.1111\/j.1447-0594.2011.00786.x"},{"key":"2025121411212004000_11.6.e050541.11","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.91.16.7772"},{"key":"2025121411212004000_11.6.e050541.12","doi-asserted-by":"publisher","DOI":"10.1016\/S0079-6123(08)00926-6"},{"key":"2025121411212004000_11.6.e050541.13","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/j.brainresbull.2017.11.001","article-title":"Vitamin A improves the symptoms of autism spectrum disorders and decreases 5-hydroxytryptamine (5-HT): a pilot study","volume":"137","author":"Guo","year":"2018","journal-title":"Brain Res Bull"},{"key":"2025121411212004000_11.6.e050541.14","doi-asserted-by":"crossref","DOI":"10.3390\/nu9121285","article-title":"The prevalence of vitamin A deficiency in Chinese children: a systematic review and Bayesian meta-analysis","volume":"9","author":"Song","year":"2017","journal-title":"Nutrients"},{"key":"2025121411212004000_11.6.e050541.15","doi-asserted-by":"publisher","DOI":"10.1016\/j.hoc.2015.11.002"},{"key":"2025121411212004000_11.6.e050541.16","doi-asserted-by":"publisher","DOI":"10.1016\/j.jsbmb.2013.11.003"},{"key":"2025121411212004000_11.6.e050541.17","doi-asserted-by":"crossref","first-page":"742","DOI":"10.2174\/1568026616666160617091559","article-title":"Retinoid X receptor selective agonists and their synthetic methods","volume":"17","author":"Wagner","year":"2017","journal-title":"Curr Top Med Chem"},{"key":"2025121411212004000_11.6.e050541.18","doi-asserted-by":"publisher","DOI":"10.1002\/JCP.24847"},{"key":"2025121411212004000_11.6.e050541.19","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.201505119"},{"key":"2025121411212004000_11.6.e050541.20","doi-asserted-by":"crossref","DOI":"10.3390\/ijms19082245","article-title":"Vitamin D in neurological diseases: a rationale for a pathogenic impact","volume":"19","author":"Moretti","year":"2018","journal-title":"Int J Mol Sci"},{"key":"2025121411212004000_11.6.e050541.21","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1016\/j.neuroscience.2016.07.020","article-title":"Vitamin D signaling and the differentiation of developing dopamine systems","volume":"333","author":"Pertile","year":"2016","journal-title":"Neuroscience"},{"key":"2025121411212004000_11.6.e050541.22","doi-asserted-by":"publisher","DOI":"10.1096\/fj.201700713R"},{"key":"2025121411212004000_11.6.e050541.23","doi-asserted-by":"crossref","first-page":"496","DOI":"10.2174\/1871527318666190703103709","article-title":"The effect of vitamin D3 supplementation on serum BDNF, dopamine, and serotonin in children with attention-deficit\/hyperactivity disorder","volume":"18","author":"Seyedi","year":"2019","journal-title":"CNS Neurol Disord Drug Targets"},{"key":"2025121411212004000_11.6.e050541.24","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1080\/09297049.2019.1665638","article-title":"Vitamin D deficiency in school-age Iranian children with attention-deficit\/hyperactivity disorder (ADHD) symptoms: a critical comparison with healthy controls","volume":"26","author":"Fasihpour","year":"2020","journal-title":"Child Neuropsychol"},{"key":"2025121411212004000_11.6.e050541.25","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1080\/1028415X.2016.1262097","article-title":"Effect of vitamin D supplementation as adjunctive therapy to methylphenidate on ADHD symptoms: a randomized, double blind, placebo-controlled trial","volume":"21","author":"Mohammadpour","year":"2018","journal-title":"Nutr Neurosci"},{"key":"2025121411212004000_11.6.e050541.26","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1007\/s12519-018-0209-8","article-title":"Effect of vitamin D treatment in children with attention-deficit hyperactivity disorder","volume":"15","author":"Dehbokri","year":"2019","journal-title":"World J Pediatr"},{"key":"2025121411212004000_11.6.e050541.27","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1177\/1060028018759471","article-title":"Impact of vitamin D supplementation on attention-deficit hyperactivity disorder in children","volume":"52","author":"Elshorbagy","year":"2018","journal-title":"Ann Pharmacother"},{"key":"2025121411212004000_11.6.e050541.28","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1016\/j.jnutbio.2015.08.020","article-title":"High vitamin A intake during pregnancy modifies dopaminergic reward system and decreases preference for sucrose in Wistar rat offspring","volume":"27","author":"S\u00e1nchez-Hern\u00e1ndez","year":"2016","journal-title":"J Nutr Biochem"},{"key":"2025121411212004000_11.6.e050541.29","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1007\/s13311-017-0581-4","article-title":"And vitamins D + A in multiple sclerosis","volume":"15","author":"Riccio","year":"2018","journal-title":"Neurotherapeutics"},{"key":"2025121411212004000_11.6.e050541.30","unstructured":"Attention Deficity disorder toolkit. Available: http:\/\/www.nccpeds.com\/adhd_toolkit.htm; [Accessed 8 May 2020]."},{"key":"2025121411212004000_11.6.e050541.31","first-page":"32","article-title":"Application of four commonly used rating scales in diagnosis and follow-up management of children with attention deficit hyperactivity disorder","volume":"45","author":"Lin","year":"2020","journal-title":"Journal of Chongqing Medical University"},{"key":"2025121411212004000_11.6.e050541.32","unstructured":"Gong Y , Cai T . Chinese-Wechsler intelligence scale for children. Chinese Journal of Clinical Psychology 1994:1\u20136."},{"key":"2025121411212004000_11.6.e050541.33","doi-asserted-by":"crossref","first-page":"2181","DOI":"10.2147\/NDT.S166397","article-title":"Reliability and validity of the Chinese version of Questionnaire - Children with Difficulties for Chinese children or adolescents with attention-deficit\/hyperactivity disorder: a cross-sectional survey","volume":"14","author":"Zheng","year":"2018","journal-title":"Neuropsychiatr Dis Treat"},{"key":"2025121411212004000_11.6.e050541.34","unstructured":"Society CN . Chinese dietary reference intakes (Chinese DRIs) (2013 edition. 322. Science Publishing House, 2014."},{"key":"2025121411212004000_11.6.e050541.35","unstructured":"Robert M , Kliegman JSG . Nelson textbook of pediatrics. 21th edn. Elsevier, 2019: 1938\u201340."},{"key":"2025121411212004000_11.6.e050541.36","unstructured":"Yonghao G , Xindong X . Pediatics.: People\u2019s Medical Publishing House Co.,LTD. 84, 2015."}],"container-title":["BMJ Open"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/bmjopen-2021-050541","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,14]],"date-time":"2025-12-14T19:21:33Z","timestamp":1765740093000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmjopen.bmj.com\/lookup\/doi\/10.1136\/bmjopen-2021-050541"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,6]]},"references-count":36,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2021,6,16]]},"published-print":{"date-parts":[[2021,6]]}},"alternative-id":["10.1136\/bmjopen-2021-050541"],"URL":"https:\/\/doi.org\/10.1136\/bmjopen-2021-050541","relation":{},"ISSN":["2044-6055","2044-6055"],"issn-type":[{"value":"2044-6055","type":"print"},{"value":"2044-6055","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,6]]}}}