{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,4]],"date-time":"2026-11-04T02:55:48Z","timestamp":1793760948158,"version":"4.6.1"},"reference-count":46,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2025,9,1]],"date-time":"2025-09-01T00:00:00Z","timestamp":1756684800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2025,9,1]],"date-time":"2025-09-01T00:00:00Z","timestamp":1756684800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2025,9,1]],"date-time":"2025-09-01T00:00:00Z","timestamp":1756684800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-017"},{"start":{"date-parts":[[2025,9,1]],"date-time":"2025-09-01T00:00:00Z","timestamp":1756684800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2025,9,1]],"date-time":"2025-09-01T00:00:00Z","timestamp":1756684800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-012"},{"start":{"date-parts":[[2025,9,1]],"date-time":"2025-09-01T00:00:00Z","timestamp":1756684800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2025,9,1]],"date-time":"2025-09-01T00:00:00Z","timestamp":1756684800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-004"}],"content-domain":{"domain":["clinicalkey.com","clinicalkey.com.au","clinicalkey.es","clinicalkey.fr","clinicalkey.jp","jns-journal.com","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Journal of the Neurological Sciences"],"published-print":{"date-parts":[[2025,9]]},"DOI":"10.1016\/j.jns.2025.123627","type":"journal-article","created":{"date-parts":[[2025,7,17]],"date-time":"2025-07-17T00:47:01Z","timestamp":1752713221000},"page":"123627","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":19,"special_numbering":"C","title":["Folate, vitamin B12, one carbon metabolism and the nervous system: Excess folic acid is potentially harmful"],"prefix":"10.1016","volume":"476","author":[{"given":"Edward H.","family":"Reynolds","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.jns.2025.123627_bb0005","doi-asserted-by":"crossref","first-page":"949","DOI":"10.1016\/S1474-4422(06)70598-1","article-title":"Vitamin B12, folic acid and the nervous system","volume":"5","author":"Reynolds","year":"2006","journal-title":"Lancet Neurol."},{"key":"10.1016\/j.jns.2025.123627_bb0010","series-title":"Handbook of Clinical Neurology. 3rd Series","doi-asserted-by":"crossref","first-page":"927","DOI":"10.1016\/B978-0-7020-4087-0.00061-9","article-title":"The neurology of folic acid deficiency","volume":"120","author":"Reynolds","year":"2014"},{"key":"10.1016\/j.jns.2025.123627_bb0015","first-page":"894","article-title":"The long term evaluation of folic acid in the treatment of pernicious anaemia","volume":"35","author":"Schwartz","year":"1950","journal-title":"J. Lab. Clin. Med."},{"key":"10.1016\/j.jns.2025.123627_bb0020","first-page":"22","article-title":"Folic acid and vitamin B12 in pernicious anaemia: studies on patients treated with these substances over a ten year period","volume":"53","author":"Will","year":"1959","journal-title":"J. Lab. Clin. Med."},{"key":"10.1016\/j.jns.2025.123627_bb0025","series-title":"Folic Acid in Neurology, Psychiatry and Internal Medicine","author":"Botez","year":"1979"},{"key":"10.1016\/j.jns.2025.123627_bb0030","doi-asserted-by":"crossref","first-page":"1036","DOI":"10.1136\/bmj.281.6247.1036","article-title":"The neuropsychiatry of megaloblastic anaemia","volume":"281","author":"Shorvon","year":"1980","journal-title":"BMJ"},{"key":"10.1016\/j.jns.2025.123627_bb0035","first-page":"17046","article-title":"Vitamin B12 deficiency","volume":"3","author":"Green","year":"2017","journal-title":"Nat. Rev. Dis. Primers."},{"key":"10.1016\/j.jns.2025.123627_bb0040","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1016\/0140-6736(91)90133-A","article-title":"Prevention of neural tube defects: results of the Medical Research Council Vitamin Study","volume":"338","author":"MRC Vitamin Study Group","year":"1991","journal-title":"Lancet"},{"key":"10.1016\/j.jns.2025.123627_bb0045","series-title":"Folate and Human Development","year":"2002"},{"key":"10.1016\/j.jns.2025.123627_bb0050","doi-asserted-by":"crossref","first-page":"k724","DOI":"10.1136\/bmj.k724","article-title":"Do the benefits of folic and fortification outweigh the risk of masking vitamin B12 deficiency?","volume":"360","author":"Mills","year":"2018","journal-title":"BMJ"},{"key":"10.1016\/j.jns.2025.123627_bb0055","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1146\/annurev-nutr-043020-091647","article-title":"Folic acid and the prevention of birth defects; 30 years of opportunity and controversies","volume":"42","author":"Crider","year":"2022","journal-title":"Annu. Rev. Nutr."},{"key":"10.1016\/j.jns.2025.123627_bb0060","series-title":"Dietary References Intakes for Thiamine, Riboflavin, Niacin, Vitamin B6, Folate, Vitamin B12, Pantothenic Acid, Biotin and Choline","first-page":"196","author":"Institute of Medicine","year":"1998"},{"key":"10.1016\/j.jns.2025.123627_bb0065","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1038\/ejcn.2015.231","article-title":"What is the safe upper intake level of folic acid for the nervous system? Implications for folic acid fortification policies","volume":"70","author":"Reynolds","year":"2016","journal-title":"Eur. J. Clin. Nutr."},{"issue":"3","key":"10.1016\/j.jns.2025.123627_bb0070","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1177\/09691413221102321","article-title":"Folic acid and neural tube defects: discovery, debate and the need for policy change","volume":"29","author":"Wald","year":"2022","journal-title":"J. Med. Screen."},{"key":"10.1016\/j.jns.2025.123627_bb0075","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1001\/jama.2023.12376","article-title":"Fully effective folic acid fortification","volume":"330","author":"Morris","year":"2023","journal-title":"JAMA"},{"key":"10.1016\/j.jns.2025.123627_bb0080","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1136\/jcp.14.4.335","article-title":"Studies on the folic acid activity of human serum","volume":"14","author":"Waters","year":"1961","journal-title":"J. Clin. Pathol."},{"key":"10.1016\/j.jns.2025.123627_bb0085","series-title":"Folic Acid in Neurology, Psychiatry and Internal Medicine","first-page":"501","article-title":"Inter-relationships between the neurology of folate and vitamin B12 metabolism","author":"Reynolds","year":"1979"},{"key":"10.1016\/j.jns.2025.123627_bb0090","doi-asserted-by":"crossref","first-page":"551","DOI":"10.3390\/jcm8040551","article-title":"Global burden related to nitrous oxide exposure in medical and recreational settings: a systematic review and individual patient data meta-analysis","volume":"8","author":"Oussalah","year":"2019","journal-title":"J. Clin. Med."},{"key":"10.1016\/j.jns.2025.123627_bb0095","doi-asserted-by":"crossref","first-page":"905","DOI":"10.1212\/WNL.26.10.905","article-title":"Neuropathology of experimental vitamin B12 deficiency in monkeys","volume":"26","author":"Agamanolis","year":"1976","journal-title":"Neurology"},{"key":"10.1016\/j.jns.2025.123627_bb0100","doi-asserted-by":"crossref","first-page":"2001","DOI":"10.1016\/0024-3205(82)90039-X","article-title":"Cobalamin inactivation by nitrous oxide produces severe neurological impairment in fruit bats: protection by methionine and aggravation by folates","volume":"31","author":"Van der Westhuvzen","year":"1982","journal-title":"Life Sci."},{"key":"10.1016\/j.jns.2025.123627_bb0105","doi-asserted-by":"crossref","first-page":"7025","DOI":"10.3945\/ajcn.2008.26947C","article-title":"Folate-vitamin B12 interaction in relation to cognitive impairment, anaemia and biochemical indicators of vitamin B12 deficiency","volume":"89","author":"Selhub","year":"2009","journal-title":"Am. J. Clin. Nutr."},{"key":"10.1016\/j.jns.2025.123627_bb0110","doi-asserted-by":"crossref","first-page":"909","DOI":"10.3233\/JAD-2011-110752","article-title":"Homocysteine, vitamin B12 and folic acid levels in Alzheimer\u2019s disease, mild cognitive impairment and healthy elderly: baseline characteristics in subjects of the Australian imaging biomarker lifestyle study","volume":"27","author":"Faux","year":"2011","journal-title":"J Alzheimer\u2019s Dis"},{"key":"10.1016\/j.jns.2025.123627_bb0115","doi-asserted-by":"crossref","first-page":"661","DOI":"10.3233\/JAD-131265","article-title":"Among vitamin B12 deficient older people, high folate levels are associated with worse cognitive function: combined data from 3 cohorts","volume":"39","author":"Moore","year":"2014","journal-title":"J. Alzheimer\u2019s Dis."},{"key":"10.1016\/j.jns.2025.123627_bb0120","doi-asserted-by":"crossref","first-page":"1547","DOI":"10.1093\/ajcn\/nqaa239","article-title":"High folic acid or folate combined with low vitamin B12 status: potential but inconsistent association with cognitive function in a nationally representative cros-sectional sample of US older adults participating in the NHANES","volume":"112","author":"Bailey","year":"2020","journal-title":"Am. J. Clin. Nutr."},{"key":"10.1016\/j.jns.2025.123627_bb0125","doi-asserted-by":"crossref","first-page":"1586","DOI":"10.3945\/ajcn.2009.27514","article-title":"Metabolic evidence of vitamin B12 deficiency, including high homocysteine and methylmalonic acid and low holotranscobalamin, is more pronounced in older adults with elevated plasma folate","volume":"90","author":"Miller","year":"2009","journal-title":"Am. J. Clin. Nutr."},{"key":"10.1016\/j.jns.2025.123627_bb0130","doi-asserted-by":"crossref","first-page":"1457","DOI":"10.1111\/j.1532-5415.2012.04076.x","article-title":"Vitamin B12 and folate status in relation to decline in scores on the mini-mental state examination in the Framlingham Heart Study","volume":"60","author":"Morris","year":"2012","journal-title":"J. Am. Geriatr. Soc."},{"key":"10.1016\/j.jns.2025.123627_bb0135","first-page":"888","article-title":"High dietary folate in pregnant mice leads to pseudo-MTHFR deficiency and altered methyl metabolism, with embryonic growth delay and short term memory impairment in offspring","volume":"26","author":"Bahous","year":"2017","journal-title":"Hum. Mol. Genet."},{"key":"10.1016\/j.jns.2025.123627_bb0140","doi-asserted-by":"crossref","first-page":"635","DOI":"10.1093\/cercor\/bhaa248","article-title":"Deficient or excess folic acid supply during pregnancy alter cortical neurodevelopment in mouse offspring","volume":"31","author":"De Crescenzo","year":"2020","journal-title":"Cereb. Cortex"},{"key":"10.1016\/j.jns.2025.123627_bb0145","doi-asserted-by":"crossref","first-page":"1123","DOI":"10.1038\/s42003-023-05492-9","article-title":"Prenatal folic acid and vitamin B12 imbalance alter neuronal morphology and synaptic density in the mouse neocortex","volume":"6","author":"Tat","year":"2023","journal-title":"Commun. Biol."},{"key":"10.1016\/j.jns.2025.123627_bb0150","doi-asserted-by":"crossref","first-page":"1051","DOI":"10.3390\/nu14051051","article-title":"Moderate folic acid supplementation in pregnant mice results in altered sex-specific gene expression in brain of young mice and embryos","volume":"14","author":"Luan","year":"2022","journal-title":"Nutrients"},{"key":"10.1016\/j.jns.2025.123627_bb0155","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1038\/s41421-022-00512-0","article-title":"Excess folic acid intake increases DNA de novo point mutations","volume":"9","author":"Cao","year":"2023","journal-title":"Cell Discov."},{"key":"10.1016\/j.jns.2025.123627_bb0160","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1038\/nrg1558","article-title":"Folic acid- vitamin and panacea or genetic timebomb?","volume":"6","author":"Lucock","year":"2005","journal-title":"Nat. Rev. Genet."},{"key":"10.1016\/j.jns.2025.123627_bb0165","first-page":"467","article-title":"Neutrigenetic determinants of neural tube defects in India","volume":"46","author":"Godbole","year":"2009","journal-title":"Ind. Paediatr."},{"key":"10.1016\/j.jns.2025.123627_bb0170","doi-asserted-by":"crossref","first-page":"1665","DOI":"10.3945\/ajcn.116.139030","article-title":"Transcobalamin 776C->G polymorphism is associated with peripheral neuropathy in elderly individuals with high folate intake","volume":"104","author":"Sawaengsri","year":"2016","journal-title":"Am. J. Clin. Nutr."},{"key":"10.1016\/j.jns.2025.123627_bb0175","doi-asserted-by":"crossref","first-page":"1603","DOI":"10.1172\/JCI40000","article-title":"Folate regulation of axonal regeneration in the rodent central nervous system through DNA methylation","volume":"120","author":"Iskandar","year":"2010","journal-title":"J. Clin. Invest."},{"key":"10.1016\/j.jns.2025.123627_bb0180","doi-asserted-by":"crossref","first-page":"2048","DOI":"10.1007\/s12035-019-01812-5","article-title":"Ancestral folate promotes neuronal regeneration in serial generations of progeny","volume":"57","author":"Patel","year":"2020","journal-title":"Mol. Neurobiol."},{"key":"10.1016\/j.jns.2025.123627_bb0185","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1111\/j.1528-1157.1971.tb03929.x","article-title":"Inter-relations of folic acid and vitamin B12 in drug-treated epileptic patients","volume":"12","author":"Reynolds","year":"1971","journal-title":"Epilepsia"},{"key":"10.1016\/j.jns.2025.123627_bb0190","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1093\/advances\/nmab106","article-title":"Perspective: the high-folate-low-vitamin B12 interaction is a novel cause of vitamin B12 depletion with a specific aetiology- a hypothesis","volume":"13","author":"Selhub","year":"2022","journal-title":"Adv. Nutr."},{"key":"10.1016\/j.jns.2025.123627_bb0195","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1038\/ejcn.2016.194","article-title":"The adverse effects of an excessive folic acid intake","volume":"71","author":"Patel","year":"2017","journal-title":"Eur. J. Clin. Nutr."},{"key":"10.1016\/j.jns.2025.123627_bb0200","first-page":"529","article-title":"Folic acid inhibits 5-methyltetrahydrofolate transport across the blood cerebrospinal fluid barrier: clinical biochemical data from 2 cases","volume":"63","author":"Akiyama","year":"2022","journal-title":"JIMD Rep."},{"key":"10.1016\/j.jns.2025.123627_bb0205","doi-asserted-by":"crossref","first-page":"2715","DOI":"10.3390\/nu14132715","article-title":"Women taking a folic acid supplement in countries with mandatory food fortification programmes may be exceeding the upper tolerable limit of folic acid: a systematic review","volume":"14","author":"Ledowsky","year":"2022","journal-title":"Nutrients"},{"key":"10.1016\/j.jns.2025.123627_bb0210","doi-asserted-by":"crossref","first-page":"657","DOI":"10.1016\/S0950-3536(05)80225-2","article-title":"Neurological complications of acquired cobalamin deficiency: clinical aspects","volume":"8","author":"Savage","year":"1995","journal-title":"Baillieres Clin. Haematol."},{"key":"10.1016\/j.jns.2025.123627_bb0215","doi-asserted-by":"crossref","first-page":"878","DOI":"10.3945\/ajcn.117.152769","article-title":"Effect of maternal high dosages of folic acid supplements on neurocognitive development in children at 4\/5 years of age: the prospective birth cohort Infancia y Medio Ambiente (INMA) study","volume":"106","author":"Valera-Gran","year":"2017","journal-title":"Am. J. Clin. Nutr."},{"key":"10.1016\/j.jns.2025.123627_bb0220","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1111\/ppe.12414","article-title":"Maternal multivitamin intake, plasma folate and vitamin B12 levels and Autism Spectrum Disorder risk in offspring","volume":"32","author":"Raghaven","year":"2018","journal-title":"Paediatr. Perinat. Epidemiol."},{"key":"10.1016\/j.jns.2025.123627_bb0225","doi-asserted-by":"crossref","first-page":"362","DOI":"10.1097\/01.ede.0000257063.77411.e9","article-title":"Vitamin B12 and the risk of neural tube defects in a folic-acid-fortified population","volume":"18","author":"Ray","year":"2007","journal-title":"Epidemiology"},{"key":"10.1016\/j.jns.2025.123627_bb0230","doi-asserted-by":"crossref","first-page":"917","DOI":"10.1542\/peds.2008-1173","article-title":"Maternal vitamin B12 status and risk of neural tube defects in a population with high neural tube defect prevalence and no folic acid fortification","volume":"123","author":"Molloy","year":"2009","journal-title":"Paediatrics"}],"container-title":["Journal of the Neurological Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0022510X25002448?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0022510X25002448?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,8,27]],"date-time":"2025-08-27T07:54:52Z","timestamp":1756281292000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0022510X25002448"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9]]},"references-count":46,"alternative-id":["S0022510X25002448"],"URL":"https:\/\/doi.org\/10.1016\/j.jns.2025.123627","relation":{},"ISSN":["0022-510X"],"issn-type":[{"value":"0022-510X","type":"print"}],"subject":[],"published":{"date-parts":[[2025,9]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Folate, vitamin B12, one carbon metabolism and the nervous system: Excess folic acid is potentially harmful","name":"articletitle","label":"Article Title"},{"value":"Journal of the Neurological Sciences","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.jns.2025.123627","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"Crown Copyright \u00a9 2025 Published by Elsevier B.V. All rights are reserved, including those for text and data mining, AI training, and similar technologies.","name":"copyright","label":"Copyright"}],"article-number":"123627"}}