Multiplex Measurement of Serum Folate Vitamers by UPLC-MS/MS
The implementation of a liquid chromatography–tandem mass spectrometry (LC-MS/MS) method to measure six folate vitamers in serum samples allows a more individual and accurate measurement than the commonly used immunoassays. In the described method, serum
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ntroduction Folate is the general term for a water-soluble B vitamin naturally found in foods such as leafy vegetables, legumes, egg yolks, liver and some citrus fruits. Folic acid itself does not occur naturally but can be obtained from vitamin supplements or by eating fortified foods [1, 2]. A number of critical cellular pathways depend on folate, including DNA, RNA, and protein methylation as well as DNA synthesis and maintenance [2, 3]. Because of this, there are many health consequences of folate deficiency among all age groups. These include megaloblastic anemia, depression, cognitive impairment, low birth weight, risk of placental abruption, neural tube defects, and other birth-related abnormalities, including orofacial clefts and heart defects [4, 5]. The most widely publicized issue surrounding folate is that of low levels during pregnancy causing birth defects associated with the nervous system. Folate is an essential micronutrient during fetal development due to its importance in transmethylation reactions and synthesis of DNA in growing cells [3]. A significant
Paul C. Guest (ed.), Multiplex Biomarker Techniques: Methods and Applications, Methods in Molecular Biology, vol. 1546, DOI 10.1007/978-1-4939-6730-8_21, © Springer Science+Business Media LLC 2017
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portion of the 300,000 neural tube defects (NTDs) that occur yearly worldwide continue to be a great public health burden although these are preventable by the periconceptual consumption of folic acid [2]. NTDs occur early in pregnancy (neural tube closure is completed by embryonic day 21–28) [6, 7] and arise when the tube fails to close properly leading to anencephaly, encephalocele and spina bifida. The demonstration that periconceptional supplementation with folic acid dramatically reduces the incidence of NTDs has generated considerable clinical and public health interest, which has led to fortification with folic acid of the food supply in the USA and some other countries [8]. The recent WHO guidelines for optimal serum and red blood cell folate levels in women of reproductive age for prevention of neural tube defects, states that in 2012 an estimated 270,358 deaths globally were attributable to congenital abnormalities during the first 28 days of life. In addition to neural tube closure, B vitamins including folate are required for brain metabolic pathways and are fundamental in all aspects of brain development and maintenance of brain health throughout life. Observational and animal evidence appears to support a role for maternal folate status in later cognitive performance of the resulting children and there are also studies linking low maternal folate status with a higher incidence of behavioral and emotional problems, inattention, and hyperactivity in the offspring [7]. Recent studies have also shown links between low plasma folate and poor cognitive performances in children and adolescents, as well as a positive association between higher dietary folate intake and academic achievement [7]. Mental dysfunction in the e
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