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Background: Little known about folates status in folate deficiency patients. This study aims to establish liquid chromatography-tandem mass spectrometry (LC-MS/MS) assay-specific reference intervals (RIs) for serum 5-Methyltetrahydrofolate (5MeTHF), folic acid (FA), 5-Formyltetrahydrofolate (5FoTHF), and total folate (TFOL), and investigate the folates status in FA-supplemented folate deficient patients.
Methods: Sera from 120 reference subjects were selected and measured. An LC-MS/MS method for serum 5MeTHF, FA, and 5FoTHF was employed. RIs were derived based on the CLSI C28-A3. Serum folate levels of 38 FA-supplemented folate deficiency patients were analyzed.
Results: RIs (median) for 5MeTHF, FA, 5FoTHF, and TFOL were 3.83-62.33 nmol/L (12.27 nmol/L), 0.30-0.92 nmol/L (0.49 nmol/L), <0.73 nmol/L (0.00 nmol/L), and 4.17-63.47 nmol/L (12.66 nmol/L), respectively. Approximately 53 % (20/38), 74 % (28/38), and 63 % (24/38) of patients presented high levels of 5MeTHF, FA, and TFOL, respectively, which far exceeded the upper reference limit (URL) of the corresponding RIs. A half (18/38) of patients showed simultaneously higher 5MeTHF and FA levels which were beyond the URLs of RIs. Near one-third (11/38) of patients exhibited extremely high FA levels which exceeded the 100-fold URL of RIs. The highest levels can be 539 nmol/L for FA, 364 nmol/L for 5MeTHF, and 686 nmol/L for TFOL.
Conclusions: LC-MS/MS assay-specific RIs were established for folates vitamers without age or gender partitioning. Abnormally high levels of unmetabolized FA and 5MeTHF were observed in quite a few FA-supplemented patients. Considering the adverse risks caused by folates excess, we appeal for a justifiable and individualized FA supplementation. We also recommend establishing LC-MS/MS assay-specific RIs for routine monitoring of folates status.
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http://dx.doi.org/10.1016/j.cca.2022.09.019 | DOI Listing |
J Nutr Biochem
June 2025
Department of Nutrition and Food Science, School of Public Health, Tianjin Medical University, Tianjin, China; Key Laboratory of Prevention and Control of Major Diseases in the Population, Ministry of Education, Tianjin Medical University, Tianjin, China; Tianjin Key Laboratory of Environment, Nutri
Folic acid (FA) can modulate neurogenesis and neural cell death, including autophagy and apoptosis, crucial for maintaining neurological homeostasis. Previous studies on the relationship between autophagy and apoptosis were contradictory, and the study aimed to investigate FA's impact on these processes in neural cells and the mechanisms involved. Three-week-old Sprague Dawley (SD) rats were divided into four dietary groups based on FA intake: FA-deficient (<0.
View Article and Find Full Text PDFAm J Physiol Gastrointest Liver Physiol
August 2025
Department of Physiology, Faculty of Pharmacy, University of Seville, Seville, Spain.
Alcohol liver damage (ALD) is increasing worldwide among adolescents, along with binge drinking (BD). BD is an acute alcohol consumption pattern, strongly pro-oxidant in the liver, and may be associated with steatosis, the first step in ALD. Folic acid (FA), an antioxidant crucial for liver function, shows compromised hepatic stores after BD.
View Article and Find Full Text PDFFASEB J
January 2024
Department of Physiology, Faculty of Pharmacy, University of Seville, Seville, Spain.
Binge drinking (BD) is an especially pro-oxidant pattern of alcohol consumption, particularly widespread in the adolescent population. In the kidneys, it affects the glomerular filtration rate (GFR), leading to high blood pressure. BD exposure also disrupts folic acid (FA) homeostasis and its antioxidant properties.
View Article and Find Full Text PDFAnimals (Basel)
October 2023
Key Laboratory of Animal Nutrition and Feed Science (Eastern of China), College of Animal Sciences, Zhejiang University, Hangzhou 310058, China.
Maternal folic acid intake has important effects on offspring growth and development. The mechanism involved in the renewal of intestinal epithelial cells remains unclear. Thus, this study aimed to investigate the potential effect of maternal folic acid supplementation during gestation and lactation on the structural and functional development of the small intestine in piglet offspring.
View Article and Find Full Text PDFFASEB J
January 2023
Research Institute of the McGill University Health Centre, Montreal, Quebec, Canada.
Epigenetic defects induced by assisted reproductive technologies (ART) have been suggested as a potential mechanism contributing to suboptimal placentation. Here, we hypothesize that ART perturbs DNA methylation (DNAme) and gene expression during early placenta development, leading to abnormal placental phenotypes observed at term. Since folic acid (FA) plays a crucial role in epigenetic regulation, we propose that FA supplementation can rescue ART-induced placental defects.
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