5-methyltetrahydrofolate

Depression is a disorder with variable presentation. Selecting treatments and dose-finding is, therefore, challenging and time-consuming. In addition, novel antidepressants such as ketamine have sparse optimization evidence. Insights obtained from metabolomics may improve the management of patients. The objective of this study was to determine whether compounds in the cerebrospinal fluid (CSF) metabolome correlate with scores on questionnaires and response to medication. We performed a retrospective pilot study to evaluate phenotypic and metabolomic variability in patients with treatment-resistant depression using multivariate data compression algorithms...

5-Methyltetrahydrofolate (5-MTHF) is the sole active form of folate functioning in the human body and is widely used as a nutraceutical. Unlike the pollution from chemical synthesis, microbial synthesis enables green production of 5-MTHF. In this study, Escherichia coli BL21 (DE3) was selected as the host. Initially, by deleting 6-phosphofructokinase 1 and overexpressing glucose-6-phosphate 1-dehydrogenase and 6-phosphogluconate dehydrogenase, the glycolysis pathway flux decreased, while the pentose phosphate pathway flux enhanced...

Methionine dependence is a characteristic of most cancer cells where they are unable to proliferate when the essential amino acid methionine is replaced with its precursor homocysteine in the growing media. Normal cells, on the other hand, thrive under these conditions and are referred to as methionine-independent. The reaction that adds a methyl group from 5-methyltetrahydrofolate to homocysteine to regenerate methionine is catalyzed by the enzyme methionine synthase with the cofactor cobalamin (vitamin B12 )...

One-carbon folate metabolites and one-carbon-related amino acids play an important role in human physiology, and their detection in biological samples is essential. However, poor stability as well as low concentrations and occurrence in different species in various biological samples make their quantification very challenging. The aim of this study was to develop a simple, fast, and sensitive ultra-high-performance liquid chromatography MS/MS (UHPLC-MS/MS) method for the simultaneous quantification of various one-carbon folate metabolites (folic acid (FA), tetrahydrofolic acid (THF), p -aminobenzoyl-L-glutamic acid (pABG), 5-formyltetrahydrofolic acid (5-CHOTHF), 5-methyltetrahydrofolic acid (5-CH3 THF), 10-formylfolic acid (10-CHOFA), 5,10-methenyl-5,6,7,8-tetrahydrofolic acid (5,10-CH+ -THF), and 4-α-hydroxy-5-methyltetrahydrofolate (hmTHF)) and one-carbon-related amino acids (homocysteine (Hcy), methionine (Met), S -ade-L-homocysteine (SAH), and S -ade-L-methionine (SAM))...

Two siblings, presenting with a neurometabolic phenotype, were identified with 5, 10-methenyltetrahydrofolate synthetase (MTHFS) deficiency. Whole genome sequencing in both patients demonstrated an homozygous MTHFS variant NM_006441.3( MTHFS ):c.434G > A, p.Arg145Gin, which has been described before. At baseline, both patients showed moderate hyperhomocysteinemia, decreased 5-methyltetrahydrofolate (5MTHF), and increased 5-formyltetrahydrofolate (5-FTHF) in whole blood. In CSF, 5MTHF levels were in the low-normal range and 5-FTHF was strongly increased...

Folate was enriched during quinoa germination, while molecular mechanisms were not well understood. In this study, three quinoa varieties were selected for germination, and changes in substrate content and enzyme activity of the folate biosynthesis pathway were monitored. 5-Methyltetrahydrofolate (5-CH3 -THF) and 5-formyltetrahydrofolate (5-CHO-THF) were significantly enriched in quinoa sprouts. Among the selected varieties, QL-2 exhibited the lowest content of the oxidation product MeFox and the highest total folate content...

B vitamins are essential for human life and their disorders can cause a variety of diseases. Solid-phase extraction (SPE) coupled to LC-MS/MS is a preferred technique for determining multiple B vitamins, however, their complexity in real biological matrices makes it hard to achieve satisfactory recovery and accuracy when simultaneous detection. In this study, a novel automated multi-cycle magnetic SPE (MSPE) coupled to the LC-MS/MS method was established using a mixed-mode anion exchange magnetic adsorbent for the simultaneous extraction of six functional B vitamins, including methylmalonic acid, riboflavin, pantothenic acid, 4-pyridoxic acid, folic acid, and 5-methyltetrahydrofolate...

OBJECTIVES: The objective of this case report was to describe the first report of FOLR1 variants associated with adult-onset paucisymptomatic leukoencephalopathy associated with cerebral folate deficiency (CFD). METHODS: Considering the patient's symptoms, a nonprogressive leukoencephalopathy was suspected. CSF 5-methyltetrahydrofolate levels were low (10 nmol/L, normal range 41-117). With no other identifiable causes, a genetic analysis was conducted, revealing a compound heterozygous FOLR1 variation (c...

Methylenetetrahydrofolate reductase (MTHFR) is a key regulatory enzyme in the one-carbon cycle. This enzyme is essential for the metabolism of methionine, folate, and RNA, as well as for the production of proteins, DNA, and RNA. MTHFR catalyses the irreversible conversion of 5,10-methylenetetrahydrofolate to its active form, 5-methyltetrahydrofolate, a co-substrate for homocysteine remethylation to methionine. Numerous variants of the MTHFR gene have been recognised, among which the C677T variant is the most extensively studied...

Cerebral folate transport deficiency, caused by a genetic defect in folate receptor α, is a devastating neurometabolic disorder that, if untreated, leads to epileptic encephalopathy, psychomotor decline and hypomyelination. Currently, there are limited data on effective dosage and duration of treatment, though early diagnosis and therapy with folinic acid appears critical. The aim of this long-term study was to identify new therapeutic approaches and novel biomarkers for assessing efficacy, focusing on myelin-sensitive MRI...

Dried blood microsampling is increasingly used for home-sampling and epidemiological studies because of its multiple advantages, including an often greatly improved analyte stability. However, a critical assessment of the stability under realistic conditions should always be performed as part of the validation, especially for unstable molecules like folates (vitamin B9). Here, the objective was to determine whether folate stability in dried blood microsamples is sufficient to allow the set-up of home-sampling studies for the monitoring of folate status in e...

Folic acid deficiency is common worldwide and is linked to an imbalance in gut microbiota. However, based on model animals used to study the utilization of folic acid by gut microbes, there are challenges of reproducibility and individual differences. In this study, an in vitro fecal slurry culture model of folic acid deficiency was established to investigate the effects of supplementation with 5-methyltetrahydrofolate (MTHF) and non-reduced folic acid (FA) on the modulation of gut microbiota. 16S rRNA sequencing results revealed that both FA (29...

OBJECTIVE: To evaluate the association of the dietary intake of food folate (natural folate) and synthetic folic acid intake from fortified foods with the risk of all-cause mortality and end-stage kidney disease (ESKD) among the chronic kidney disease (CKD) population in regions with folic acid fortification. METHODS: 4028 individuals with established CKD in Chronic Renal Insufficiency Cohort (CRIC) were included. Diet was assessed using a validated diet history questionnaire at the baseline, year 2, and year 4, and nutrient intake, including food folate and folic acid from fortified foods, was estimated using the National Nutrient Database...

The level of vitamin B group in human serum is an important index of human health. Among B vitamins, cyanocobalamin in serum is unstable and its content is extremely low. Rapid and simultaneous detection of multiple B vitamins including cyanocobalamin is a challenge. Herein, we have developed a rapid and stable method that can realize the determination of thiamine, riboflavin, nicotinamide, pantothenic acid, pyridoxic acid, biotin, 5-methyltetrahydrofolate, and cyanocobalamin simultaneously in 6 min. The method was established based on protein precipitation with methanol and then chromatographic separation was achieved using Waters acquity ultra-high-performance liquid chromatography high strength silica T3 column, which was stable and sensitive especially for cyanocobalamin...

BACKGROUND: Most studies have explored the relationship between serum total folate and nonalcoholic fatty liver disease (NAFLD) in adults, but there has been no study on the relationship between different folate forms and hepatic steatosis or liver stiffness in adolescents. OBJECTIVE: To investigate the association of different folate forms with hepatic steatosis or liver stiffness in adolescents, and further explore the intermediary role of BMI in this relationship...

Folate deficiency contribute to neural tube defects (NTDs) which could be rescued by folate supplementation. However, the underlying mechanisms are still not fully understood. Besides, there is considerable controversy concerning the forms of folate used for supplementation. To address this controversy, we prepared culture medium with different forms of folate, folic acid (FA), and 5-methyltetrahydrofolate (5mTHF), at concentrations of 5 μM, 500 nM, 50 nM, and folate free, respectively...

BACKGROUND: Folic acid (FA) is the oxidized form of folate found in supplements and FA-fortified foods. Most FA is reduced by dihydrofolate reductase to 5-methyltetrahydrofolate (5mTHF); the latter is the form of folate naturally found in foods. Ingestion of FA increases the plasma levels of both 5mTHF and unmetabolized FA (UMFA). Limited information is available on the downstream metabolic effects of FA supplementation, including potential effects associated with UMFA. OBJECTIVE: We aimed to assess the metabolic effects of FA-supplementation, and the associations of plasma 5mTHF and UMFA with the metabolome in FA-naïve Bangladeshi adults...

With the rapid advancement of medical technologies in genomic and molecular medicine, the number of treatable neurometabolic diseases is quickly expanding. Spastic paraplegia 56 (SPG56), one of the severe autosomal recessive forms of neurodegenerative disorders caused by pathogenic variants in the CYP2U1 gene, has no reported specific targeted treatment yet. Here we report 2 Chinese brothers with CYP2U1 bi-allelic pathogenic variants with cerebral folate deficiency who were treated for over a decade with folinic acid supplement...

Supplementation with folic acid versus (6S)-5-methyltetrahydrofolic acid (5-MTHF) results in different folate forms in human milk, with folic acid increasing unmetabolized folic acid (UMFA) at the expense of reduced folate forms. It is unknown whether folate forms present in human milk have further effects on human milk composition, such as human milk oligosaccharide (HMO) concentrations. We randomized 60 pregnant women in Canada to 0.6 mg/day folic acid or (6S)-5-MTHF. Human milk folate forms (LC-MS/MS) and nineteen HMOs (HPLC) were quantified at 1 week postpartum...

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on monosodium salt of l-5-methyltetrahydrofolic acid (5-MTHF) as a novel food (NF) pursuant to Regulation (EU) 2015/2283 and to address the bioavailability of folate from this source in the context of Directive 2002/46/EC, Regulation (EU) No 609/2013 and Regulation (EC) No 1925/2006. The NF is produced by chemical synthesis and consists of at least 95% (w/w) of 5-MTHF and 4%-5% (w/w) of sodium...