{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:22:05Z","timestamp":1787026925577,"version":"build-2736575974"},"reference-count":49,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,9,30]],"date-time":"2021-09-30T00:00:00Z","timestamp":1632960000000},"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:p>\n                    <jats:bold>Objective:<\/jats:bold>\n                    The vitamin K family has a wide range of effects in the body, including the central nervous system. Menaquinone-4 (MK-4), a form of vitamin K2, is converted from phylloquinone (PK), which is the main source of dietary vitamin K and is the main form of vitamin K in the brain. We conducted this study to investigate the serum concentration of MK-4 and the correlations between MK-4 and developmental quotients in children with autism spectrum disorder (ASD).\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Methods:<\/jats:bold>\n                    We selected 731 children with ASD who were diagnosed for the first time. During the same period, 332 neurotypical children who underwent regular physical examinations in our outpatient department were selected as the TD group. We investigated the general situation of children, including gender and age. Children in ASD group were assessed for autistic symptoms and development quotients, including Autism Behavior Checklist (ABC), Childhood Autism Rating Scale (CARS), ADOS-2, and Griffiths Development Scales-Chinese Language Edition (GDS-C). Both groups of children were tested for serum menaquinone-4. We compared serum menaquinone-4 levels of ASD group and TD group. We then conducted a correlation analysis between the level of menaquinone-4 and the developmental quotient of children with ASD.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Results:<\/jats:bold>\n                    The results of this study indicate that the serum concentration of MK-4 in children with ASD is lower than that in children with typical development (\n                    <jats:italic>t<\/jats:italic>\n                    = \u22122.702,\n                    <jats:italic>P<\/jats:italic>\n                    = 0.007). The serum concentration of MK-4 is related to the developmental quotients of several subscales in ASD children, and this correlation is more obvious in males.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Conclusion:<\/jats:bold>\n                    we conclude that MK-4 is present in lower concentrations in children with ASD, which may affect cognition and developmental quotients. The role of MK-4 in ASD needs to be further explored.\n                  <\/jats:p>","DOI":"10.3389\/fnut.2021.748513","type":"journal-article","created":{"date-parts":[[2021,9,30]],"date-time":"2021-09-30T01:23:34Z","timestamp":1632965014000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":7,"title":["Correlation Between Serum Concentrations of Menaquinone-4 and Developmental Quotients in Children With Autism Spectrum Disorder"],"prefix":"10.3389","volume":"8","author":[{"given":"Hanyu","family":"Dong","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bing","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junyan","family":"Feng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaojing","family":"Yue","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feiyong","family":"Jia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,9,30]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"151","DOI":"10.1002\/biof.1004","article-title":"Vitamin K, an emerging nutrient in brain function","volume":"38","author":"Ferland","year":"2012","journal-title":"Biofactors"},{"key":"B2","doi-asserted-by":"publisher","first-page":"11270","DOI":"10.1074\/jbc.M702971200","article-title":"Conversion of phylloquinone (Vitamin K1) into menaquinone-4 (Vitamin K2) in mice: two possible routes for menaquinone-4 accumulation in cerebra of mice","volume":"283","author":"Okano","year":"2008","journal-title":"J Biol Chem"},{"key":"B3","doi-asserted-by":"publisher","first-page":"117","DOI":"10.1038\/nature09464","article-title":"Identification of UBIAD1 as a novel human menaquinone-4 biosynthetic enzyme","volume":"468","author":"Nakagawa","year":"2010","journal-title":"Nature"},{"key":"B4","doi-asserted-by":"publisher","first-page":"204","DOI":"10.3945\/an.111.001784","article-title":"Vitamin K and the nervous system: an overview of its actions","volume":"3","author":"Ferland","year":"2012","journal-title":"Adv Nutr."},{"key":"B5","doi-asserted-by":"publisher","first-page":"167","DOI":"10.1093\/jn\/134.1.167","article-title":"Menaquinone-4 concentration is correlated with sphingolipid concentrations in rat brain","volume":"134","author":"Carri\u00e9","year":"2004","journal-title":"J Nutr."},{"key":"B6","doi-asserted-by":"publisher","first-page":"613","DOI":"10.1124\/mol.112.082602","article-title":"Vitamin K2 covalently binds to Bak and induces Bak-mediated apoptosis","volume":"83","author":"Karasawa","year":"2013","journal-title":"Mol Pharmacol."},{"key":"B7","doi-asserted-by":"publisher","first-page":"849","DOI":"10.1055\/s-0033-1357481","article-title":"Vitamin K and brain function","volume":"39","author":"Ferland","year":"2013","journal-title":"Semin Thromb Hemost."},{"key":"B8","doi-asserted-by":"crossref","first-page":"1475","DOI":"10.1016\/S0022-2275(20)38426-1","article-title":"Warfarin administration reduces synthesis of sulfatides and other sphingolipids in mouse brain","volume":"29","author":"Sundaram","year":"1988","journal-title":"J Lipid Res."},{"key":"B9","doi-asserted-by":"publisher","first-page":"358","DOI":"10.1016\/0006-291x(71)90826-6","article-title":"Vitamin K stimulation of sphingolipid synthesis","volume":"45","author":"Lev","year":"1971","journal-title":"Biochem Biophys Res Commun"},{"key":"B10","doi-asserted-by":"publisher","first-page":"327","DOI":"10.1016\/j.molmed.2007.06.002","article-title":"Translational aspects of sphingolipid metabolism","volume":"13","author":"Zeidan","year":"2007","journal-title":"Trends Mol Med."},{"key":"B11","doi-asserted-by":"publisher","first-page":"2070","DOI":"10.1073\/pnas.0305799101","article-title":"Involvement of oxidative stress-induced abnormalities in ceramide and cholesterol metabolism in brain aging and Alzheimer's disease","volume":"101","author":"Cutler","year":"2004","journal-title":"Proc Natl Acad Sci USA."},{"key":"B12","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1016\/j.jns.2008.12.010","article-title":"Ceramide and neurodegeneration: susceptibility of neurons and oligodendrocytes to cell damage and death","volume":"278","author":"Jana","year":"2009","journal-title":"J Neurol Sci."},{"key":"B13","doi-asserted-by":"publisher","first-page":"1748","DOI":"10.1016\/j.febslet.2009.12.010","article-title":"Sphingolipids and gangliosides of the nervous system in membrane function and dysfunction","volume":"584","author":"Posse de Chaves","year":"2010","journal-title":"FEBS Lett."},{"key":"B14","doi-asserted-by":"publisher","first-page":"4976","DOI":"10.1128\/mcb.13.8.4976-4985.1993","article-title":"The protein encoded by a growth arrest-specific gene (gas6) is a new member of the vitamin K-dependent proteins related to protein S, a negative coregulator in the blood coagulation cascade","volume":"13","author":"Manfioletti","year":"1993","journal-title":"Mol Cell Biol"},{"key":"B15","doi-asserted-by":"publisher","first-page":"623","DOI":"10.1038\/373623a0","article-title":"Axl receptor tyrosine kinase stimulated by the vitamin K-dependent protein encoded by growth-arrest-specific gene 6","volume":"373","author":"Varnum","year":"1995","journal-title":"Nature"},{"key":"B16","doi-asserted-by":"publisher","first-page":"5638","DOI":"10.1523\/jneurosci.5063-05.2006","article-title":"Gas6\/Axl signaling activates the phosphatidylinositol 3-kinase\/Akt1 survival pathway to protect oligodendrocytes from tumor necrosis factor alpha-induced apoptosis","volume":"26","author":"Shankar","year":"2006","journal-title":"J Neurosci."},{"key":"B17","doi-asserted-by":"publisher","first-page":"174","DOI":"10.1016\/s0002-9610(97)89590-6","article-title":"Continuous arteriovenous hemofiltration attenuates polymorphonuclear leukocyte phagocytosis in porcine intra-abdominal sepsis","volume":"173","author":"DiScipio","year":"1997","journal-title":"Am J Surg."},{"key":"B18","doi-asserted-by":"publisher","first-page":"2307","DOI":"10.1182\/blood-2009-03-209031","article-title":"Generation and phenotypic analysis of protein S-deficient mice","volume":"114","author":"Saller","year":"2009","journal-title":"Blood."},{"key":"B19","doi-asserted-by":"publisher","first-page":"1997","DOI":"10.1002\/jnr.22029","article-title":"Vitamin K prevents oxidative cell death by inhibiting activation of 12-lipoxygenase in developing oligodendrocytes","volume":"87","author":"Li","year":"2009","journal-title":"J Neurosci Res."},{"key":"B20","doi-asserted-by":"publisher","first-page":"313","DOI":"10.1093\/aje\/kwm306;","article-title":"Vitamin K and vitamin D status: associations with inflammatory markers in the Framingham Offspring Study","volume":"167","author":"Shea","year":"2008","journal-title":"Am J Epidemiol."},{"key":"B21","doi-asserted-by":"publisher","first-page":"356","DOI":"10.1093\/ajcn\/88.2.356","article-title":"Vitamin K, circulating cytokines, and bone mineral density in older men and women","volume":"88","author":"Shea","year":"2008","journal-title":"Am J Clin Nutr."},{"key":"B22","first-page":"217","article-title":"Autistic disturbances of affective contact","volume":"2","author":"Kanner","year":"1943","journal-title":"Pathology"},{"key":"B23","doi-asserted-by":"publisher","first-page":"1","DOI":"10.15585\/mmwr.ss6904a1","article-title":"Prevalence of autism spectrum disorder among children aged 8 years - autism and developmental disabilities monitoring network, 11 sites, United States 2016","volume":"69","author":"Maenner","year":"2020","journal-title":"MMWR Surveill Summ"},{"key":"B24","doi-asserted-by":"publisher","first-page":"204","DOI":"10.1080\/13668250601006924","article-title":"Dietary status and impact of risperidone on nutritional balance in children with autism: a pilot study","volume":"31","author":"Lindsay","year":"2006","journal-title":"J Intellect Dev Disabil."},{"key":"B25","doi-asserted-by":"publisher","first-page":"34","DOI":"10.1186\/1743-7075-8-34","article-title":"Nutritional and metabolic status of children with autism vs. neurotypical children, and the association with autism severity","volume":"8","author":"Adams","year":"2011","journal-title":"Nutr Metab."},{"key":"B26","doi-asserted-by":"publisher","first-page":"1193","DOI":"10.1007\/s00787-018-1143-y","article-title":"Diagnostic accuracy of the ADOS and ADOS-2 in clinical practice","volume":"27","author":"Kamp-Becker","year":"2018","journal-title":"Eur Child Adolesc Psychiatry."},{"key":"B27","doi-asserted-by":"publisher","first-page":"102144","DOI":"10.1016\/j.ajp.2020.102144","article-title":"The Griffiths Development Scales-Chinese (GDS-C): A reliable and valid neurodevelopmental assessment tool in children with ASD aged 3-8 years old in Tianjin, China","volume":"52","author":"Li","year":"2020","journal-title":"Asian J Psychiatr."},{"key":"B28","doi-asserted-by":"publisher","first-page":"321","DOI":"10.1111\/j.1365-2214.2005.00505.x","article-title":"Standardization of the motor scales of the Griffiths Test II on children aged 3 to 6 years in Greece","volume":"31","author":"Giagazoglou","year":"2005","journal-title":"Child Care Health Dev."},{"key":"B29","doi-asserted-by":"publisher","first-page":"1029","DOI":"10.3945\/jn.109.118380","article-title":"Adulthood obesity is positively associated with adipose tissue concentrations of vitamin K and inversely associated with circulating indicators of vitamin K status in men and women","volume":"140","author":"Shea","year":"2010","journal-title":"J Nutr."},{"key":"B30","doi-asserted-by":"publisher","first-page":"1046","DOI":"10.1177\/1362361318791817","article-title":"Prevalence of overweight and obesity among US youth with autism spectrum disorder","volume":"23","author":"Healy","year":"2019","journal-title":"Autism."},{"key":"B31","doi-asserted-by":"publisher","first-page":"627011","DOI":"10.3389\/fnut.2021.627011","article-title":"Nutritional status of pre-school children and determinant factors of autism: a case-control study","volume":"8","author":"Alkhalidy","year":"2021","journal-title":"Front Nutr."},{"key":"B32","doi-asserted-by":"publisher","first-page":"303","DOI":"10.1254\/jjp.46.303","article-title":"Vitamin K-reversible hypoprothrombinemia in rats. I. Sex differences in the development of hypoprothrombinemia and the effects of beta-lactam antibiotics","volume":"46","author":"Matsuura","year":"1988","journal-title":"Jpn J Pharmacol."},{"key":"B33","doi-asserted-by":"publisher","first-page":"172","DOI":"10.1001\/jamacardio.2016.0199;","article-title":"Outcomes in a warfarin-treated population with atrial fibrillation","volume":"1","author":"Bj\u00f6rck","year":"2016","journal-title":"JAMA Cardiol."},{"key":"B34","doi-asserted-by":"publisher","first-page":"151","DOI":"10.1007\/s11239-007-0048-2","article-title":"Incidence and predictors of severe bleeding during warfarin treatment","volume":"25","author":"Lindh","year":"2008","journal-title":"J Thromb Thrombolysis."},{"key":"B35","doi-asserted-by":"publisher","first-page":"867","DOI":"10.1007\/s00228-020-02856-6","article-title":"Risk factors for severe bleeding events during warfarin treatment: the influence of sex, age, comorbidity and co-medication","volume":"76","author":"Rydberg","year":"2020","journal-title":"Eur J Clin Pharmacol."},{"key":"B36","doi-asserted-by":"publisher","first-page":"107","DOI":"10.1159\/000157104","article-title":"Mechanism of bone and cartilage maldevelopment in the warfarin embryopathy","volume":"7","author":"Pauli","year":"1988","journal-title":"Pathol Immunopathol Res"},{"key":"B37","doi-asserted-by":"publisher","first-page":"122","DOI":"10.1016\/0002-9343(80)90181-3","article-title":"Maternal and fetal sequelae of anticoagulation during pregnancy","volume":"68","author":"Hall","year":"1980","journal-title":"Am J Med."},{"key":"B38","doi-asserted-by":"publisher","first-page":"2095","DOI":"10.1016\/j.jada.2008.09.013","article-title":"Low vitamin K intakes in community-dwelling elders at an early stage of Alzheimer's disease","volume":"108","author":"Presse","year":"2008","journal-title":"J Am Diet Assoc."},{"key":"B39","doi-asserted-by":"publisher","first-page":"131","DOI":"10.1016\/j.maturitas.2016.02.004","article-title":"Increased dietary vitamin K intake is associated with less severe subjective memory complaint among older adults","volume":"93","author":"Soutif-Veillon","year":"2016","journal-title":"Maturitas."},{"key":"B40","doi-asserted-by":"publisher","first-page":"727","DOI":"10.1016\/0031-9384(85)90371-3","article-title":"Behavioral perturbations in the vitamin K-deficient rat","volume":"34","author":"Cocchetto","year":"1985","journal-title":"Physiol Behav."},{"key":"B41","doi-asserted-by":"publisher","first-page":"82","DOI":"10.1093\/jn\/nxz200","article-title":"Concentrations of circulating phylloquinone, but not cerebral menaquinone-4, are positively correlated with a wide range of cognitive measures: exploratory findings in centenarians","volume":"150","author":"Tanprasertsuk","year":"2020","journal-title":"J Nutr."},{"key":"B42","doi-asserted-by":"publisher","first-page":"67","DOI":"10.1016\/j.ntt.2012.07.006","article-title":"Cytokine dysregulation in autism spectrum disorders (ASD): possible role of the environment","volume":"36","author":"Goines","year":"2013","journal-title":"Neurotoxicol Teratol."},{"key":"B43","doi-asserted-by":"publisher","first-page":"120","DOI":"10.1016\/j.cyto.2018.03.034","article-title":"Cytokine profile in autistic patients","volume":"108","author":"Eftekharian","year":"2018","journal-title":"Cytokine"},{"key":"B44","doi-asserted-by":"publisher","first-page":"67","DOI":"10.1189\/jlb.0811427","article-title":"Mechanisms of sex disparities in influenza pathogenesis","volume":"92","author":"Klein","year":"2012","journal-title":"J Leukoc Biol."},{"key":"B45","doi-asserted-by":"publisher","first-page":"838","DOI":"10.1016\/j.biopsych.2016.05.011","article-title":"Excitation\/inhibition imbalance in animal models of autism spectrum disorders","volume":"81","author":"Lee","year":"2017","journal-title":"Biol Psychiatry."},{"key":"B46","doi-asserted-by":"publisher","first-page":"587","DOI":"10.2174\/1871527315666160413121751","article-title":"Oxidative stress and nitric oxide in autism spectrum disorder and other neuropsychiatric disorders","volume":"15","author":"Yui","year":"2016","journal-title":"CNS Neurol Disord Drug Targets."},{"key":"B47","doi-asserted-by":"publisher","first-page":"331","DOI":"10.1007\/s00401-017-1718-6","article-title":"White matter injury in the preterm infant: pathology and mechanisms","volume":"134","author":"Back","year":"2017","journal-title":"Acta Neuropathol."},{"key":"B48","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1111\/j.1471-4159.2008.05570.x","article-title":"The life, death, and replacement of oligodendrocytes in the adult CNS","volume":"107","author":"McTigue","year":"2008","journal-title":"J Neurochem."},{"key":"B49","doi-asserted-by":"publisher","first-page":"e0203057","DOI":"10.1371\/journal.pone.0203057","article-title":"Vitamin K enhances the production of brain sulfatides during remyelination","volume":"13","author":"Popescu","year":"2018","journal-title":"PLoS ONE."}],"container-title":["Frontiers in Nutrition"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnut.2021.748513\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,9,30]],"date-time":"2021-09-30T01:23:37Z","timestamp":1632965017000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnut.2021.748513\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,9,30]]},"references-count":49,"alternative-id":["10.3389\/fnut.2021.748513"],"URL":"https:\/\/doi.org\/10.3389\/fnut.2021.748513","relation":{},"ISSN":["2296-861X"],"issn-type":[{"value":"2296-861X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,9,30]]},"article-number":"748513"}}