{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T03:51:16Z","timestamp":1790135476092,"version":"4.0.1"},"reference-count":174,"publisher":"Walter de Gruyter GmbH","issue":"9","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2017,1,28]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Several authors have recently claimed an excess in serum folate test ordering, suggesting phasing out it from clinical use. According to studies performed in countries undergoing folic acid fortification policies, it is indeed no more cost-effective to test folate in the face of deficiency prevalence &lt;1%. In this paper, we sought to evaluate request appropriateness, analytical issues, and cost-effectiveness of serum folate determination for clinical purposes in the European context, considering if evidence retrieved in fortified countries may be generalized. Studies performed in non-fortified countries have generally reported a suboptimal folate intake and suggest a remarkable prevalence of folate deficiency. Our internal data suggest that ~20%\u201325% of the subjects undergoing serum folate test are at risk for deficiency. However, a reliable evaluation of the risk for deficiency implies the knowledge of all issues related to the total testing process of folate measurement as well as the identification of the appropriate population in which to perform the test. The cost-effectiveness of the test is maximized when the request is oriented to subjects suggestive\/at risk for deficiency, becoming low if the test is used as a screening tool or for monitoring of vitamin intake\/supplementation. Because the individual folate status has a key role in ensuring normal development, physiologic growth, and maintenance of optimal health, the evaluation of its serum levels has to be retained in the clinical use in non-fortified countries, boosting for more appropriate request, and evidence from countries following fortification policies should be cautionary interpreted.<\/jats:p>","DOI":"10.1515\/cclm-2016-0804","type":"journal-article","created":{"date-parts":[[2016,12,18]],"date-time":"2016-12-18T10:01:15Z","timestamp":1482055275000},"source":"Crossref","is-referenced-by-count":22,"title":["Tackling serum folate test in European countries within the health technology assessment paradigm: request appropriateness, assays and health outcomes"],"prefix":"10.1515","volume":"55","author":[{"given":"Simona","family":"Ferraro","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Panzeri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mauro","family":"Panteghini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"374","reference":[{"key":"ref1081","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1016\/j.reprotox.2015.04.009","article-title":"Maternal predictors of RBC folate levels in an urban Canadian population","volume":"53","year":"2015","journal-title":"Reprod Toxicol"},{"key":"ref1331","doi-asserted-by":"crossref","first-page":"584","DOI":"10.1038\/sj.ejcn.1602112","article-title":"Dietary habits, lifestyle and cardiovascular risk factors in a clinically healthy Italian population: the \u2018Florence\u2019 diet is not Mediterranean","volume":"59","year":"2005","journal-title":"Eur J Clin Nutr"},{"key":"ref1541","first-page":"986","article-title":"Isotope dilution-LC-MS\/MS reference method assessment of serum folate assay accuracy and proficiency testing consensus mean","volume":"57","year":"2011","journal-title":"Clin Chem Lab Med"},{"key":"ref1191","article-title":"Folic acid supplementation may reduce colorectal cancer risk in patients with inflammatory bowel disease: a systematic review and meta-analysis","year":"2016","journal-title":"J Clin Gastroenterol"},{"key":"ref1571","doi-asserted-by":"crossref","first-page":"684","DOI":"10.1373\/clinchem.2004.042358","article-title":"Issues in immunoassay standardization: the Architect folate model for intermethod harmonization","volume":"51","year":"2005","journal-title":"Clin Chem"},{"key":"ref691","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1002\/ajh.2830260211","article-title":"Making sense of laboratory tests of folate status: folate requirements to sustain normality","volume":"26","year":"1987","journal-title":"Am J Hematol"},{"key":"ref1561","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1093\/clinchem\/21.3.427","article-title":"pH dependence of the binding of folate to milk binder in radioassay of folates","volume":"21","year":"1975","journal-title":"Clin Chem"},{"key":"ref1021","doi-asserted-by":"crossref","first-page":"1003","DOI":"10.1016\/S1701-2163(16)32685-8","article-title":"Pre-conception vitamin\/folic acid supplementation 2007: the use of folic acid in combination with a multivitamin supplement for the prevention of neural tube defects and other congenital anomalies","volume":"29","year":"2007","journal-title":"J Obstet Gynaecol Can"},{"key":"ref361","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1016\/j.numecd.2011.10.001","article-title":"Folate, vitamin B12 and homocysteine status in an Italian blood donor population","volume":"23","year":"2013","journal-title":"Nutr Metab Cardiovasc Dis"},{"key":"ref1601","doi-asserted-by":"crossref","first-page":"2486","DOI":"10.1001\/jama.2008.742","article-title":"Contributions of total daily intake of folic acid to serum folate concentrations","volume":"300","year":"2008","journal-title":"J Am Med Assoc"},{"key":"ref351","first-page":"694","article-title":"Folate status in Italian blood donors: relation to gender and smoking","volume":"85","year":"2000","journal-title":"Haematologica"},{"key":"ref1741","doi-asserted-by":"crossref","first-page":"1237","DOI":"10.1515\/cclm.2011.791","article-title":"Implementation of standardization in clinical practice: not always an easy task","volume":"50","year":"2012","journal-title":"Clin Chem Lab Med"},{"key":"ref601","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1042\/bj1930469","article-title":"The preparation and properties of folate-binding protein from cow\u2019s milk","volume":"193","year":"1981","journal-title":"Biochem J"},{"key":"ref951","doi-asserted-by":"crossref","first-page":"1696","DOI":"10.1001\/jamainternmed.2014.3593","article-title":"Low yield of outpatient serum folate testing: eleven years of experience","volume":"174","year":"2014","journal-title":"JAMA Intern Med"},{"key":"ref1471","doi-asserted-by":"crossref","first-page":"231","DOI":"10.3945\/ajcn.2009.28427","article-title":"Total folate and folic acid intake from foods and dietary supplements in the United States: 2003\u20132006","volume":"91","year":"2010","journal-title":"Am J Clin Nutr"},{"key":"ref661","doi-asserted-by":"crossref","first-page":"718","DOI":"10.1093\/ajcn\/86.3.718","article-title":"Trends in blood folate and vitamin B-12 concentrations in the United States, 1988\u20132004","volume":"86","year":"2007","journal-title":"Am J Clin Nutr"},{"key":"ref191","journal-title":"Clinical utility of serum folate measurement in tertiary care patients. Argument for revising reference range for serum folate from 3.0 ng\/mL to 13 ng\/mL"},{"key":"ref761","volume-title":"National minimum re-testing interval project. Prepared for the Clinical Practice Group of the ACB and supported by the Royal College of Pathologists","year":"2013"},{"key":"ref1771","doi-asserted-by":"crossref","first-page":"1352","DOI":"10.1016\/S0140-6736(06)68582-6","article-title":"Folic acid: a public-health challenge","volume":"367","year":"2006","journal-title":"Lancet"},{"key":"ref331","doi-asserted-by":"crossref","first-page":"1159","DOI":"10.1111\/j.1468-1331.2012.03784.x","article-title":"EFNS-ENS guidelines on the diagnosis and management of disorders associated with dementia","volume":"19","year":"2012","journal-title":"Eur J Neurol"},{"key":"ref1851","doi-asserted-by":"crossref","first-page":"383","DOI":"10.3945\/ajcn.2010.29499","article-title":"Unmetabolized serum folic acid and its relation to folic acid intake from diet and supplements in a nationally representative sample of adults aged 60 y in the United States","volume":"92","year":"2010","journal-title":"Am J Clin Nutr"},{"key":"ref31","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1016\/j.amjmed.2014.08.020","article-title":"Folate testing in hospital inpatients","volume":"128","year":"2015","journal-title":"Am J Med"},{"key":"ref1751","doi-asserted-by":"crossref","first-page":"1911","DOI":"10.1515\/cclm-2012-0129","article-title":"Revaluating serum ferritin as a marker of body iron stores in the traceability era","volume":"50","year":"2012","journal-title":"Clin Chem Lab Med"},{"key":"ref1521","first-page":"S459","article-title":"Recoveries of folate species from serum pools sent to participants in the UK NEQAS Haematinics Scheme in February and March 2004","volume":"355","year":"2005","journal-title":"Clin Chim Acta"},{"key":"ref231","doi-asserted-by":"crossref","first-page":"1029","DOI":"10.1016\/S0140-6736(12)62001-7","article-title":"B-Vitamin Treatment Trialists\u2019 Collaboration. Effects of folic acid supplementation on overall and site-specific cancer incidence during the randomised trials: meta-analyses of data on 50,000 individuals","volume":"381","year":"2013","journal-title":"Lancet"},{"key":"ref21","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1002\/jhm.1994","article-title":"Utility, charge, and cost of inpatient and emergency department serum folate testing","volume":"8","year":"2013","journal-title":"J Hosp Med"},{"key":"ref1891","doi-asserted-by":"crossref","first-page":"777","DOI":"10.1136\/jclinpath-2015-203447","article-title":"Computer-based-limited and personalised education management maximise appropriateness of vitamin D, vitamin B12 and folate retesting","volume":"69","year":"2016","journal-title":"J Clin Pathol"},{"key":"ref1371","first-page":"1","article-title":"Updated estimates of neural tube defects prevented by mandatory folic acid fortification \u2013 United States, 1995\u20132011","volume":"64","year":"2015","journal-title":"Morb Mortal Wkly Rep"},{"key":"ref581","first-page":"423","article-title":"Determination of folate vitamers in human serum by stable-isotope-dilution tandem mass spectrometry and comparison with radioassay and microbiologic assay","volume":"50","year":"2004","journal-title":"Clin Chem Lab Med"},{"key":"ref461","first-page":"36","article-title":"EUnetHTA and health policy-making in Europe","volume":"12","year":"2006","journal-title":"Eurohealth"},{"key":"ref1591","first-page":"1579","article-title":"Results of an international round robin for serum and whole blood folate","volume":"42","year":"1996","journal-title":"Clin Chem Lab Med"},{"key":"ref1641","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1002\/ajh.2830260211","article-title":"Making sense of laboratory tests of folate status: folate requirements to sustain normality","volume":"26","year":"1987","journal-title":"Am J Hematol"},{"key":"ref731","doi-asserted-by":"crossref","first-page":"313","DOI":"10.3109\/10408363.2016.1150252","article-title":"Generation of data on within-subject biological variation in laboratory medicine: an update","volume":"53","year":"2016","journal-title":"Crit Rev Clin Lab Sci"},{"key":"ref11","doi-asserted-by":"crossref","first-page":"1697","DOI":"10.1001\/jamainternmed.2014.3272","article-title":"Folate testing: time to retire your VCR","volume":"174","year":"2014","journal-title":"JAMA Intern Med"},{"key":"ref911","journal-title":"Folic acid: from research to public health practice"},{"key":"ref1031","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1016\/S0002-9343(00)00670-7","article-title":"Lack of clinical utility of folate levels in the evaluation of macrocytosis or anemia","volume":"110","year":"2001","journal-title":"Am J Med"},{"key":"ref1181","doi-asserted-by":"crossref","first-page":"1029","DOI":"10.1016\/S0140-6736(12)62001-7","article-title":"B-Vitamin Treatment Trialists\u2019 Collaboration. Effects of folic acid supplementation on overall and site-specific cancer incidence during the randomised trials: meta-analyses of data on 50,000 individuals","volume":"381","year":"2013","journal-title":"Lancet"},{"key":"ref1581","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1309\/L2U6HH5KAYG48L40","article-title":"Comparison of five automated serum and whole blood folate assays","volume":"120","year":"2003","journal-title":"Am J Clin Pathol"},{"key":"ref531","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1373\/clinchem.2007.096545","article-title":"Influence of 5,10-methylenetetrahydrofolate reductase polymorphism on whole-blood folate concentrations measured by LC-MS\/MS, microbiologic assay, and Bio-Rad radioassay","volume":"54","year":"2008","journal-title":"Clin Chem"},{"key":"ref1511","first-page":"380","article-title":"International standard for serum vitamin B12 and serum folate: international collaborative study to evaluate a batch of lyophilised serum for B12 and folate content","volume":"45","year":"2007","journal-title":"Clin Chem Lab Med"},{"key":"ref671","doi-asserted-by":"crossref","first-page":"1405","DOI":"10.1093\/ajcn\/86.5.1405","article-title":"Effect of a voluntary food fortification policy on folate, related B vitamin status, and homocysteine in healthy adults","volume":"86","year":"2007","journal-title":"Am J Clin Nutr"},{"key":"ref541","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1093\/clinchem\/44.1.186a","article-title":"Whole-blood folate values in subjects with different methylenetetrahydrofolate reductase genotypes: differences between the radioassay and microbiological assays","volume":"44","year":"1998","journal-title":"Clin Chem"},{"key":"ref1681","doi-asserted-by":"crossref","first-page":"313","DOI":"10.3109\/10408363.2016.1150252","article-title":"Generation of data on within-subject biological variation in laboratory medicine: an update","volume":"53","year":"2016","journal-title":"Crit Rev Clin Lab Sci"},{"key":"ref81","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1016\/S0002-9343(00)00670-7","article-title":"Lack of clinical utility of folate levels in the evaluation of macrocytosis or anemia","volume":"110","year":"2001","journal-title":"Am J Med"},{"key":"ref971","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1002\/jhm.1994","article-title":"Utility, charge, and cost of inpatient and emergency department serum folate testing","volume":"8","year":"2013","journal-title":"J Hosp Med"},{"key":"ref1291","doi-asserted-by":"crossref","first-page":"1236","DOI":"10.1111\/j.1468-1331.2010.03040.x","article-title":"EFNS guidelines for the diagnosis and management of Alzheimer\u2019s disease","volume":"17","year":"2010","journal-title":"Eur J Neurol"},{"key":"ref1861","journal-title":"Folic acid: from research to public health practice"},{"key":"ref621","doi-asserted-by":"crossref","first-page":"684","DOI":"10.1373\/clinchem.2004.042358","article-title":"Issues in immunoassay standardization: the Architect folate model for intermethod harmonization","volume":"51","year":"2005","journal-title":"Clin Chem"},{"key":"ref251","doi-asserted-by":"crossref","first-page":"1636S","DOI":"10.3945\/jn.114.206599","article-title":"Biomarkers of nutrition for development-Folate review","volume":"145","year":"2015","journal-title":"J Nutr"},{"key":"ref1821","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1093\/jn\/136.1.189","article-title":"Unmetabolized folic acid in plasma is associated with reduced natural killer cell cytotoxicity among postmenopausal women","volume":"136","year":"2006","journal-title":"J Nutr"},{"key":"ref1441","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1016\/j.jchromb.2009.11.021","article-title":"Quantification of key folate forms in serum using stable-isotope dilution ultra performance liquid chromatography-tandem mass spectrometry","volume":"878","year":"2010","journal-title":"J Chrom B"},{"key":"ref921","journal-title":"Gene-environment interactions: folates and congenital malformations"},{"key":"ref181","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1136\/gut.45.3.389","article-title":"Increased prevalence of methylenetetrahydrofolate reductase C677T variant in patients with inflammatory bowel disease, and its clinical implications","volume":"45","year":"1999","journal-title":"Gut"},{"key":"ref271","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1038\/sj.ejcn.1602897","article-title":"Dietary intake and status of folate and vitamin B12 and their association with homocysteine and cardiovascular disease in European populations","volume":"63","year":"2009","journal-title":"Eur J Clin Nutr"},{"key":"ref901","doi-asserted-by":"crossref","first-page":"383","DOI":"10.3945\/ajcn.2010.29499","article-title":"Unmetabolized serum folic acid and its relation to folic acid intake from diet and supplements in a nationally representative sample of adults aged 60 y in the United States","volume":"92","year":"2010","journal-title":"Am J Clin Nutr"},{"key":"ref571","first-page":"S459","article-title":"Recoveries of folate species from serum pools sent to participants in the UK NEQAS Haematinics Scheme in February and March 2004","volume":"355","year":"2005","journal-title":"Clin Chim Acta"},{"key":"ref1141","journal-title":"Clinical utility of serum folate measurement in tertiary care patients. Argument for revising reference range for serum folate from 3.0 ng\/mL to 13 ng\/mL"},{"key":"ref1451","doi-asserted-by":"crossref","first-page":"1147","DOI":"10.1373\/clinchem.2008.114389","article-title":"Liquid chromatography\u2013 tandem mass spectrometry analysis of folate and folate catabolites in human serum","volume":"55","year":"2009","journal-title":"Clin Chem"},{"key":"ref241","article-title":"Folic acid supplementation may reduce colorectal cancer risk in patients with inflammatory bowel disease: a systematic review and meta-analysis","year":"2016","journal-title":"J Clin Gastroenterol"},{"key":"ref471","doi-asserted-by":"crossref","first-page":"1965","DOI":"10.1017\/S0007114515001142","article-title":"Folate status and concentrations of serum folate forms in the US population: National Health and Nutrition Examination Survey 2011-2","volume":"113","year":"2015","journal-title":"Br J Nutr"},{"key":"ref91","doi-asserted-by":"crossref","first-page":"1079","DOI":"10.3945\/ajcn.111.020230","article-title":"Vitamin B-12 and homocysteine status in a folate-replete population: results from the Canadian Health Measures Survey","volume":"94","year":"2011","journal-title":"Am J Clin Nutr"},{"key":"ref101","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1111\/j.1365-2257.2004.00649.x","article-title":"Is there a role for folate determinations in current practice in the USA?","volume":"26","year":"2004","journal-title":"Clin Lab Haematol"},{"key":"ref701","doi-asserted-by":"crossref","first-page":"S67","DOI":"10.1177\/15648265080292S110","article-title":"The use of blood concentrations of vitamins and their respective functional indicators to define folate and vitamin B12 status","volume":"29","year":"2008","journal-title":"Food Nutr Bull"},{"key":"ref41","doi-asserted-by":"crossref","first-page":"533","DOI":"10.1016\/j.clinbiochem.2014.01.023","article-title":"Utility of measuring serum or red blood cell folate in the era of folate fortification of flour","volume":"47","year":"2014","journal-title":"Clin Biochem"},{"key":"ref961","doi-asserted-by":"crossref","first-page":"1697","DOI":"10.1001\/jamainternmed.2014.3272","article-title":"Folate testing: time to retire your VCR","volume":"174","year":"2014","journal-title":"JAMA Intern Med"},{"key":"ref321","doi-asserted-by":"crossref","first-page":"886","DOI":"10.3945\/jn.111.156919","article-title":"Estimation of trends in serum and RBC folate in the U.S. population from pre- to post-fortification using assay-adjusted data from the NHANES 1988-2010","volume":"142","year":"2012","journal-title":"J Nutr"},{"key":"ref561","first-page":"380","article-title":"International standard for serum vitamin B12 and serum folate: international collaborative study to evaluate a batch of lyophilised serum for B12 and folate content","volume":"45","year":"2007","journal-title":"Clin Chem Lab Med"},{"key":"ref821","doi-asserted-by":"crossref","first-page":"1352","DOI":"10.1016\/S0140-6736(06)68582-6","article-title":"Folic acid: a public-health challenge","volume":"367","year":"2006","journal-title":"Lancet"},{"key":"ref801","doi-asserted-by":"crossref","first-page":"1911","DOI":"10.1515\/cclm-2012-0129","article-title":"Revaluating serum ferritin as a marker of body iron stores in the traceability era","volume":"50","year":"2012","journal-title":"Clin Chem Lab Med"},{"key":"ref01","doi-asserted-by":"crossref","first-page":"1696","DOI":"10.1001\/jamainternmed.2014.3593","article-title":"Low yield of outpatient serum folate testing: eleven years of experience","volume":"174","year":"2014","journal-title":"JAMA Intern Med"},{"key":"ref1551","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1042\/bj1930469","article-title":"The preparation and properties of folate-binding protein from cow\u2019s milk","volume":"193","year":"1981","journal-title":"Biochem J"},{"key":"ref841","first-page":"i734","article-title":"Decision on folic acid fortification in Europe must consider both risks and benefits","volume":"352","year":"2016","journal-title":"Br Med J"},{"key":"ref1111","doi-asserted-by":"crossref","first-page":"3498","DOI":"10.1111\/j.1572-0241.2000.03367.x","article-title":"Increased levels of homocysteine in patients with Crohn\u2019s disease are related to folate levels","volume":"95","year":"2000","journal-title":"Am J Gastroenterol"},{"key":"ref211","doi-asserted-by":"crossref","first-page":"1325","DOI":"10.1158\/1055-9965.EPI-07-0329","article-title":"A temporal association between folic acid fortification and an increase in colorectal cancer rates may be illuminating important biological principles: a hypothesis","volume":"16","year":"2007","journal-title":"Cancer Epidemiol Biomark Prev"},{"key":"ref1201","doi-asserted-by":"crossref","first-page":"1636S","DOI":"10.3945\/jn.114.206599","article-title":"Biomarkers of nutrition for development-Folate review","volume":"145","year":"2015","journal-title":"J Nutr"},{"key":"ref371","first-page":"S32","article-title":"SENECA Investigators. Changes in the vitamin status of elderly Europeans: plasma vitamins A, E, B-6, B-12, folic acid and carotenoids","volume":"50","year":"1996","journal-title":"Eur J Clin Nutr"},{"key":"ref1171","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1016\/S0027-5107(01)00079-3","article-title":"The role of folic acid and vitamin B12 in genomic stability of human cells","volume":"475","year":"2001","journal-title":"Mutat Res"},{"key":"ref1311","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1016\/j.numecd.2011.10.001","article-title":"Folate, vitamin B12 and homocysteine status in an Italian blood donor population","volume":"23","year":"2013","journal-title":"Nutr Metab Cardiovasc Dis"},{"key":"ref1071","first-page":"e100","article-title":"Low clinical utility of folate determinations in primary care","volume":"19","year":"2013","journal-title":"Am J Manag Care"},{"key":"ref1361","journal-title":"Riflessioni sulla prevenzione primaria dei difetti del tubo neurale in Italia e spunti per una raccomandazione basata sulle evidenze pi\u00f9 recenti"},{"key":"ref711","doi-asserted-by":"crossref","first-page":"S238","DOI":"10.1177\/15648265080292S129","article-title":"Conclusions of a WHO Technical Consultation on folate and vitamin B12 deficiencies","volume":"29","year":"2008","journal-title":"Food Nutr Bull"},{"key":"ref1241","doi-asserted-by":"crossref","first-page":"4760","DOI":"10.3390\/nu5114760","article-title":"Folate deficiency and folic acid supplementation: the prevention of neural-tube defects and congenital heart defects","volume":"5","year":"2013","journal-title":"Nutrients"},{"key":"ref1281","doi-asserted-by":"crossref","first-page":"1159","DOI":"10.1111\/j.1468-1331.2012.03784.x","article-title":"EFNS-ENS guidelines on the diagnosis and management of disorders associated with dementia","volume":"19","year":"2012","journal-title":"Eur J Neurol"},{"key":"ref1051","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1111\/j.1365-2257.2004.00649.x","article-title":"Is there a role for folate determinations in current practice in the USA?","volume":"26","year":"2004","journal-title":"Clin Lab Haematol"},{"key":"ref451","journal-title":"Health technology assessment and health policy-making in Europe. Current status, challenges and potential"},{"key":"ref1121","doi-asserted-by":"crossref","first-page":"658","DOI":"10.1093\/rheumatology\/41.6.658","article-title":"Homocysteine and folate status in methotrexate-treated patients with rheumatoid arthritis","volume":"41","year":"2002","journal-title":"Rheumatology"},{"key":"ref881","first-page":"h5949","article-title":"Long term trends in prevalence of neural tube defects in Europe: population based study","volume":"351","year":"2015","journal-title":"Br Med J"},{"key":"ref941","doi-asserted-by":"crossref","first-page":"777","DOI":"10.1136\/jclinpath-2015-203447","article-title":"Computer-based-limited and personalised education management maximise appropriateness of vitamin D, vitamin B12 and folate retesting","volume":"69","year":"2016","journal-title":"J Clin Pathol"},{"key":"ref981","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1016\/j.amjmed.2014.08.020","article-title":"Folate testing in hospital inpatients","volume":"128","year":"2015","journal-title":"Am J Med"},{"key":"ref121","first-page":"e100","article-title":"Low clinical utility of folate determinations in primary care","volume":"19","year":"2013","journal-title":"Am J Manag Care"},{"key":"ref1761","first-page":"767","article-title":"Tracing a roadmap for vitamin B12 testing using the health technology assessment approach","volume":"52","year":"2014","journal-title":"Clin Chem Lab Med"},{"key":"ref681","doi-asserted-by":"crossref","first-page":"1873","DOI":"10.3945\/jn.114.198358","article-title":"The loss of 5-methyltetrahydrofolate in human serum under suboptimal preanalytical conditions can only partially be recovered by an oxidation product","volume":"144","year":"2014","journal-title":"J Nutr"},{"key":"ref1611","doi-asserted-by":"crossref","first-page":"718","DOI":"10.1093\/ajcn\/86.3.718","article-title":"Trends in blood folate and vitamin B-12 concentrations in the United States, 1988\u20132004","volume":"86","year":"2007","journal-title":"Am J Clin Nutr"},{"key":"ref431","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1017\/S1368980008002565","article-title":"A cost-effectiveness analysis of folic acid fortification policy in the United States","volume":"12","year":"2009","journal-title":"Public Health Nutr"},{"key":"ref141","doi-asserted-by":"crossref","first-page":"957S","DOI":"10.3945\/jn.112.173021","article-title":"Dietary supplement use and smoking are important correlates of biomarkers of water-soluble vitamin status after adjusting for sociodemographic and lifestyle variables in a representative sample of U.S. adults","volume":"143","year":"2013","journal-title":"J Nutr"},{"key":"ref171","doi-asserted-by":"crossref","first-page":"658","DOI":"10.1093\/rheumatology\/41.6.658","article-title":"Homocysteine and folate status in methotrexate-treated patients with rheumatoid arthritis","volume":"41","year":"2002","journal-title":"Rheumatology"},{"key":"ref991","doi-asserted-by":"crossref","first-page":"533","DOI":"10.1016\/j.clinbiochem.2014.01.023","article-title":"Utility of measuring serum or red blood cell folate in the era of folate fortification of flour","volume":"47","year":"2014","journal-title":"Clin Biochem"},{"key":"ref1271","doi-asserted-by":"crossref","first-page":"886","DOI":"10.3945\/jn.111.156919","article-title":"Estimation of trends in serum and RBC folate in the U.S. population from pre- to post-fortification using assay-adjusted data from the NHANES 1988-2010","volume":"142","year":"2012","journal-title":"J Nutr"},{"key":"ref1431","doi-asserted-by":"crossref","first-page":"2378","DOI":"10.1373\/clinchem.2004.036541","article-title":"Measurement of folates in serum and conventionally prepared whole blood lysates: application of an automated 96-well plate isotope-dilution tandem mass spectrometry method","volume":"50","year":"2004","journal-title":"Clin Chem"},{"key":"ref1791","first-page":"i734","article-title":"Decision on folic acid fortification in Europe must consider both risks and benefits","volume":"352","year":"2016","journal-title":"Br Med J"},{"key":"ref1661","doi-asserted-by":"crossref","first-page":"S238","DOI":"10.1177\/15648265080292S129","article-title":"Conclusions of a WHO Technical Consultation on folate and vitamin B12 deficiencies","volume":"29","year":"2008","journal-title":"Food Nutr Bull"},{"key":"ref1321","first-page":"S32","article-title":"SENECA Investigators. Changes in the vitamin status of elderly Europeans: plasma vitamins A, E, B-6, B-12, folic acid and carotenoids","volume":"50","year":"1996","journal-title":"Eur J Clin Nutr"},{"key":"ref1211","first-page":"653","article-title":"Laboratory medicine as the science that underpins medicine: the \u201chigh-sensitivity\u201d troponin paradigm","volume":"53","year":"2015","journal-title":"Clin Chem Lab Med"},{"key":"ref341","doi-asserted-by":"crossref","first-page":"1236","DOI":"10.1111\/j.1468-1331.2010.03040.x","article-title":"EFNS guidelines for the diagnosis and management of Alzheimer\u2019s disease","volume":"17","year":"2010","journal-title":"Eur J Neurol"},{"key":"ref651","doi-asserted-by":"crossref","first-page":"2486","DOI":"10.1001\/jama.2008.742","article-title":"Contributions of total daily intake of folic acid to serum folate concentrations","volume":"300","year":"2008","journal-title":"J Am Med Assoc"},{"key":"ref311","first-page":"h6198","article-title":"Folic acid fortification for Europe?","volume":"351","year":"2015","journal-title":"Br Med J"},{"key":"ref1131","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1136\/gut.45.3.389","article-title":"Increased prevalence of methylenetetrahydrofolate reductase C677T variant in patients with inflammatory bowel disease, and its clinical implications","volume":"45","year":"1999","journal-title":"Gut"},{"key":"ref781","first-page":"1289","article-title":"The new European Directive on in vitro diagnostics","volume":"41","year":"2003","journal-title":"Clin Chem Lab Med"},{"key":"ref1631","doi-asserted-by":"crossref","first-page":"1873","DOI":"10.3945\/jn.114.198358","article-title":"The loss of 5-methyltetrahydrofolate in human serum under suboptimal preanalytical conditions can only partially be recovered by an oxidation product","volume":"144","year":"2014","journal-title":"J Nutr"},{"key":"ref591","first-page":"986","article-title":"Isotope dilution-LC-MS\/MS reference method assessment of serum folate assay accuracy and proficiency testing consensus mean","volume":"57","year":"2011","journal-title":"Clin Chem Lab Med"},{"key":"ref1691","first-page":"11","volume-title":"Hematology in clinical practice","year":"2005"},{"key":"ref71","doi-asserted-by":"crossref","first-page":"1003","DOI":"10.1016\/S1701-2163(16)32685-8","article-title":"Pre-conception vitamin\/folic acid supplementation 2007: the use of folic acid in combination with a multivitamin supplement for the prevention of neural tube defects and other congenital anomalies","volume":"29","year":"2007","journal-title":"J Obstet Gynaecol Can"},{"key":"ref491","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1016\/j.jchromb.2009.11.021","article-title":"Quantification of key folate forms in serum using stable-isotope dilution ultra performance liquid chromatography-tandem mass spectrometry","volume":"878","year":"2010","journal-title":"J Chrom B"},{"key":"ref1101","doi-asserted-by":"crossref","first-page":"320","DOI":"10.1016\/j.ejim.2010.05.007","article-title":"Serum vitamin B12 and folate status in patients with inflammatory bowel diseases","volume":"21","year":"2010","journal-title":"Eur J Intern Med"},{"key":"ref1871","journal-title":"Gene-environment interactions: folates and congenital malformations"},{"key":"ref1401","journal-title":"Health technology assessment and health policy-making in Europe. Current status, challenges and potential"},{"key":"ref301","first-page":"132","article-title":"IANA task force on nutrition and cognitive decline with aging","volume":"11","year":"2007","journal-title":"J Nutr Health Aging"},{"key":"ref1531","first-page":"423","article-title":"Determination of folate vitamers in human serum by stable-isotope-dilution tandem mass spectrometry and comparison with radioassay and microbiologic assay","volume":"50","year":"2004","journal-title":"Clin Chem Lab Med"},{"key":"ref831","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1016\/S0020-7489(99)00003-6","article-title":"Medication compliance and older people: a review of the literature","volume":"36","year":"1999","journal-title":"Int J Nurs Stud"},{"key":"ref1831","first-page":"h5949","article-title":"Long term trends in prevalence of neural tube defects in Europe: population based study","volume":"351","year":"2015","journal-title":"Br Med J"},{"key":"ref521","doi-asserted-by":"crossref","first-page":"231","DOI":"10.3945\/ajcn.2009.28427","article-title":"Total folate and folic acid intake from foods and dietary supplements in the United States: 2003\u20132006","volume":"91","year":"2010","journal-title":"Am J Clin Nutr"},{"key":"ref631","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1309\/L2U6HH5KAYG48L40","article-title":"Comparison of five automated serum and whole blood folate assays","volume":"120","year":"2003","journal-title":"Am J Clin Pathol"},{"key":"ref1351","doi-asserted-by":"crossref","first-page":"2057","DOI":"10.1016\/S0140-6736(06)68917-4","article-title":"Folic acid: a public-health challenge","volume":"367","year":"2006","journal-title":"Lancet"},{"key":"ref1781","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1016\/S0020-7489(99)00003-6","article-title":"Medication compliance and older people: a review of the literature","volume":"36","year":"1999","journal-title":"Int J Nurs Stud"},{"key":"ref1711","volume-title":"National minimum re-testing interval project. Prepared for the Clinical Practice Group of the ACB and supported by the Royal College of Pathologists","year":"2013"},{"key":"ref1671","volume-title":"Biological variation of laboratory analytes based on the 1999\u20132002 National Health and Nutrition Examination Survey. National health statistics reports; no. 21","year":"2010"},{"key":"ref281","doi-asserted-by":"crossref","first-page":"1281","DOI":"10.1093\/jn\/133.5.1281","article-title":"The interaction between MTHFR 677 C-->T genotype and folate status is a determinant of coronary atherosclerosis risk","volume":"133","year":"2003","journal-title":"J Nutr"},{"key":"ref1231","doi-asserted-by":"crossref","first-page":"1281","DOI":"10.1093\/jn\/133.5.1281","article-title":"The interaction between MTHFR 677 C-->T genotype and folate status is a determinant of coronary atherosclerosis risk","volume":"133","year":"2003","journal-title":"J Nutr"},{"key":"ref221","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1016\/S0027-5107(01)00079-3","article-title":"The role of folic acid and vitamin B12 in genomic stability of human cells","volume":"475","year":"2001","journal-title":"Mutat Res"},{"key":"ref891","doi-asserted-by":"crossref","first-page":"S38","DOI":"10.1177\/15648265080292S107","article-title":"Review of the magnitude of folate and vitamin B12 deficiencies worldwide","volume":"29","year":"2008","journal-title":"Food Nutr Bull"},{"key":"ref641","first-page":"1579","article-title":"Results of an international round robin for serum and whole blood folate","volume":"42","year":"1996","journal-title":"Clin Chem Lab Med"},{"key":"ref1161","doi-asserted-by":"crossref","first-page":"1325","DOI":"10.1158\/1055-9965.EPI-07-0329","article-title":"A temporal association between folic acid fortification and an increase in colorectal cancer rates may be illuminating important biological principles: a hypothesis","volume":"16","year":"2007","journal-title":"Cancer Epidemiol Biomark Prev"},{"key":"ref871","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1093\/jn\/136.1.189","article-title":"Unmetabolized folic acid in plasma is associated with reduced natural killer cell cytotoxicity among postmenopausal women","volume":"136","year":"2006","journal-title":"J Nutr"},{"key":"ref1011","volume-title":"Memorandum. Laboratory utilization: folate testing is no longer justified in folic acid fortified countries","year":"2012"},{"key":"ref1381","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1017\/S1368980008002565","article-title":"A cost-effectiveness analysis of folic acid fortification policy in the United States","volume":"12","year":"2009","journal-title":"Public Health Nutr"},{"key":"ref751","doi-asserted-by":"crossref","first-page":"448","DOI":"10.1093\/ajcn\/88.2.448","article-title":"Folate status and homocysteine response to folic acid doses and withdrawal among young Chinese women in a large-scale randomized double-blind trial","volume":"88","year":"2008","journal-title":"Am J Clin Nutr"},{"key":"ref1481","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1373\/clinchem.2007.096545","article-title":"Influence of 5,10-methylenetetrahydrofolate reductase polymorphism on whole-blood folate concentrations measured by LC-MS\/MS, microbiologic assay, and Bio-Rad radioassay","volume":"54","year":"2008","journal-title":"Clin Chem"},{"key":"ref161","doi-asserted-by":"crossref","first-page":"3498","DOI":"10.1111\/j.1572-0241.2000.03367.x","article-title":"Increased levels of homocysteine in patients with Crohn\u2019s disease are related to folate levels","volume":"95","year":"2000","journal-title":"Am J Gastroenterol"},{"key":"ref501","doi-asserted-by":"crossref","first-page":"1147","DOI":"10.1373\/clinchem.2008.114389","article-title":"Liquid chromatography\u2013 tandem mass spectrometry analysis of folate and folate catabolites in human serum","volume":"55","year":"2009","journal-title":"Clin Chem"},{"key":"ref1391","doi-asserted-by":"crossref","first-page":"303","DOI":"10.3945\/ajcn.111.013011","article-title":"Biomarkers of folate status in NHANES: a roundtable summary","volume":"94","year":"2011","journal-title":"Am J Clin Nutr"},{"key":"ref291","doi-asserted-by":"crossref","first-page":"4760","DOI":"10.3390\/nu5114760","article-title":"Folate deficiency and folic acid supplementation: the prevention of neural-tube defects and congenital heart defects","volume":"5","year":"2013","journal-title":"Nutrients"},{"key":"ref741","first-page":"11","volume-title":"Hematology in clinical practice","year":"2005"},{"key":"ref1701","doi-asserted-by":"crossref","first-page":"448","DOI":"10.1093\/ajcn\/88.2.448","article-title":"Folate status and homocysteine response to folic acid doses and withdrawal among young Chinese women in a large-scale randomized double-blind trial","volume":"88","year":"2008","journal-title":"Am J Clin Nutr"},{"key":"ref441","doi-asserted-by":"crossref","first-page":"303","DOI":"10.3945\/ajcn.111.013011","article-title":"Biomarkers of folate status in NHANES: a roundtable summary","volume":"94","year":"2011","journal-title":"Am J Clin Nutr"},{"key":"ref771","doi-asserted-by":"crossref","first-page":"1371S","DOI":"10.1093\/jn\/125.5.1371S","article-title":"Assessment of folate methodology used in the Third National Health and Nutrition Examination Survey (NHANESIII, 1988\u20131994)","volume":"125","year":"1995","journal-title":"J Nutr"},{"key":"ref1421","doi-asserted-by":"crossref","first-page":"1965","DOI":"10.1017\/S0007114515001142","article-title":"Folate status and concentrations of serum folate forms in the US population: National Health and Nutrition Examination Survey 2011-2","volume":"113","year":"2015","journal-title":"Br J Nutr"},{"key":"ref811","first-page":"767","article-title":"Tracing a roadmap for vitamin B12 testing using the health technology assessment approach","volume":"52","year":"2014","journal-title":"Clin Chem Lab Med"},{"key":"ref1261","first-page":"h6198","article-title":"Folic acid fortification for Europe?","volume":"351","year":"2015","journal-title":"Br Med J"},{"key":"ref421","first-page":"1","article-title":"Updated estimates of neural tube defects prevented by mandatory folic acid fortification \u2013 United States, 1995\u20132011","volume":"64","year":"2015","journal-title":"Morb Mortal Wkly Rep"},{"key":"ref1621","doi-asserted-by":"crossref","first-page":"1405","DOI":"10.1093\/ajcn\/86.5.1405","article-title":"Effect of a voluntary food fortification policy on folate, related B vitamin status, and homocysteine in healthy adults","volume":"86","year":"2007","journal-title":"Am J Clin Nutr"},{"key":"ref1301","first-page":"694","article-title":"Folate status in Italian blood donors: relation to gender and smoking","volume":"85","year":"2000","journal-title":"Haematologica"},{"key":"ref1721","doi-asserted-by":"crossref","first-page":"1371S","DOI":"10.1093\/jn\/125.5.1371S","article-title":"Assessment of folate methodology used in the Third National Health and Nutrition Examination Survey (NHANESIII, 1988\u20131994)","volume":"125","year":"1995","journal-title":"J Nutr"},{"key":"ref1411","first-page":"36","article-title":"EUnetHTA and health policy-making in Europe","volume":"12","year":"2006","journal-title":"Eurohealth"},{"key":"ref261","first-page":"653","article-title":"Laboratory medicine as the science that underpins medicine: the \u201chigh-sensitivity\u201d troponin paradigm","volume":"53","year":"2015","journal-title":"Clin Chem Lab Med"},{"key":"ref1221","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1038\/sj.ejcn.1602897","article-title":"Dietary intake and status of folate and vitamin B12 and their association with homocysteine and cardiovascular disease in European populations","volume":"63","year":"2009","journal-title":"Eur J Clin Nutr"},{"key":"ref151","doi-asserted-by":"crossref","first-page":"320","DOI":"10.1016\/j.ejim.2010.05.007","article-title":"Serum vitamin B12 and folate status in patients with inflammatory bowel diseases","volume":"21","year":"2010","journal-title":"Eur J Intern Med"},{"key":"ref401","doi-asserted-by":"crossref","first-page":"2057","DOI":"10.1016\/S0140-6736(06)68917-4","article-title":"Folic acid: a public-health challenge","volume":"367","year":"2006","journal-title":"Lancet"},{"key":"ref411","journal-title":"Riflessioni sulla prevenzione primaria dei difetti del tubo neurale in Italia e spunti per una raccomandazione basata sulle evidenze pi\u00f9 recenti"},{"key":"ref611","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1093\/clinchem\/21.3.427","article-title":"pH dependence of the binding of folate to milk binder in radioassay of folates","volume":"21","year":"1975","journal-title":"Clin Chem"},{"key":"ref1461","doi-asserted-by":"crossref","first-page":"763","DOI":"10.1093\/ajcn\/88.3.763","article-title":"Circulating folic acid in plasma: relation to folic acid fortification","volume":"88","year":"2008","journal-title":"Am J Clin Nutr"},{"key":"ref721","volume-title":"Biological variation of laboratory analytes based on the 1999\u20132002 National Health and Nutrition Examination Survey. National health statistics reports; no. 21","year":"2010"},{"key":"ref481","doi-asserted-by":"crossref","first-page":"2378","DOI":"10.1373\/clinchem.2004.036541","article-title":"Measurement of folates in serum and conventionally prepared whole blood lysates: application of an automated 96-well plate isotope-dilution tandem mass spectrometry method","volume":"50","year":"2004","journal-title":"Clin Chem"},{"key":"ref511","doi-asserted-by":"crossref","first-page":"763","DOI":"10.1093\/ajcn\/88.3.763","article-title":"Circulating folic acid in plasma: relation to folic acid fortification","volume":"88","year":"2008","journal-title":"Am J Clin Nutr"},{"key":"ref791","doi-asserted-by":"crossref","first-page":"1237","DOI":"10.1515\/cclm.2011.791","article-title":"Implementation of standardization in clinical practice: not always an easy task","volume":"50","year":"2012","journal-title":"Clin Chem Lab Med"},{"key":"ref131","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1016\/j.reprotox.2015.04.009","article-title":"Maternal predictors of RBC folate levels in an urban Canadian population","volume":"53","year":"2015","journal-title":"Reprod Toxicol"},{"key":"ref381","doi-asserted-by":"crossref","first-page":"584","DOI":"10.1038\/sj.ejcn.1602112","article-title":"Dietary habits, lifestyle and cardiovascular risk factors in a clinically healthy Italian population: the \u2018Florence\u2019 diet is not Mediterranean","volume":"59","year":"2005","journal-title":"Eur J Clin Nutr"},{"key":"ref1841","doi-asserted-by":"crossref","first-page":"S38","DOI":"10.1177\/15648265080292S107","article-title":"Review of the magnitude of folate and vitamin B12 deficiencies worldwide","volume":"29","year":"2008","journal-title":"Food Nutr Bull"},{"key":"ref1251","first-page":"132","article-title":"IANA task force on nutrition and cognitive decline with aging","volume":"11","year":"2007","journal-title":"J Nutr Health Aging"},{"key":"ref1651","doi-asserted-by":"crossref","first-page":"S67","DOI":"10.1177\/15648265080292S110","article-title":"The use of blood concentrations of vitamins and their respective functional indicators to define folate and vitamin B12 status","volume":"29","year":"2008","journal-title":"Food Nutr Bull"},{"key":"ref61","volume-title":"Memorandum. Laboratory utilization: folate testing is no longer justified in folic acid fortified countries","year":"2012"},{"key":"ref1041","doi-asserted-by":"crossref","first-page":"1079","DOI":"10.3945\/ajcn.111.020230","article-title":"Vitamin B-12 and homocysteine status in a folate-replete population: results from the Canadian Health Measures Survey","volume":"94","year":"2011","journal-title":"Am J Clin Nutr"},{"key":"ref1731","first-page":"1289","article-title":"The new European Directive on in vitro diagnostics","volume":"41","year":"2003","journal-title":"Clin Chem Lab Med"},{"key":"ref1091","doi-asserted-by":"crossref","first-page":"957S","DOI":"10.3945\/jn.112.173021","article-title":"Dietary supplement use and smoking are important correlates of biomarkers of water-soluble vitamin status after adjusting for sociodemographic and lifestyle variables in a representative sample of U.S. adults","volume":"143","year":"2013","journal-title":"J Nutr"},{"key":"ref1491","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1093\/clinchem\/44.1.186a","article-title":"Whole-blood folate values in subjects with different methylenetetrahydrofolate reductase genotypes: differences between the radioassay and microbiological assays","volume":"44","year":"1998","journal-title":"Clin Chem"}],"container-title":["Clinical Chemistry and Laboratory Medicine (CCLM)"],"original-title":[],"link":[{"URL":"http:\/\/www.degruyter.com\/view\/j\/cclm.2017.55.issue-9\/cclm-2016-0804\/cclm-2016-0804.xml","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.degruyter.com\/document\/doi\/10.1515\/cclm-2016-0804\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,7,17]],"date-time":"2022-07-17T18:37:13Z","timestamp":1658083033000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.degruyter.com\/document\/doi\/10.1515\/cclm-2016-0804\/html"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,1,1]]},"references-count":174,"journal-issue":{"issue":"9"},"URL":"https:\/\/doi.org\/10.1515\/cclm-2016-0804","relation":{},"ISSN":["1437-4331","1434-6621"],"issn-type":[{"value":"1437-4331","type":"electronic"},{"value":"1434-6621","type":"print"}],"subject":[],"published":{"date-parts":[[2017,1,1]]}}}