U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry ABSOLUTE
Molecular Formula C20H23N7O6.2Na
Molecular Weight 503.4195
Optical Activity UNSPECIFIED
Defined Stereocenters 2 / 2
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of LEVOMEFOLATE SODIUM

SMILES

[Na+].[Na+].CN1[C@@H](CNC2=CC=C(C=C2)C(=O)N[C@@H](CCC([O-])=O)C([O-])=O)CNC3=NC(N)=NC(O)=C13

InChI

InChIKey=KKIWVYLOTHCGRV-NJHZPMQHSA-L
InChI=1S/C20H25N7O6.2Na/c1-27-12(9-23-16-15(27)18(31)26-20(21)25-16)8-22-11-4-2-10(3-5-11)17(30)24-13(19(32)33)6-7-14(28)29;;/h2-5,12-13,22H,6-9H2,1H3,(H,24,30)(H,28,29)(H,32,33)(H4,21,23,25,26,31);;/q;2*+1/p-2/t12-,13-;;/m0../s1

HIDE SMILES / InChI
For people with MTHFR gene variations, supplementing with the already activated form of folate (5-MTHF/5- METHYLTETRAHYDROFOLATE/LEVOMEFOLIC ACID) is far more effective in providing this form of folate than introducing the pre-converted form to the body through typical folate supplements. L-Methylfolate (5-MTHF) supplements provide the active form of folate naturally present in the body and available for biological action. 5-MTHF—the “active” form of folate that is able to pass the blood brain barrier. However, without a properly functioning methylenetetrahydrofolate reductase, MTHFR this conversion cannot take place and folate is not converted to forms that can cross the blood brain barrier. That is where 5-MTHF supplements come in. Levomefolate calcium is structurally identical to L-5-methyltetrahydrofolate (L-5-methyl-THF), a metabolite of vitamin B9. Mean baseline concentrations of about 15 nmol/L are reached in populations without folate food fortification under normal nutritional conditions. Orally administered levomefolate calcium is absorbed and is incorporated into the body folate pool. Peak plasma concentrations of about 50 nmol/L above baseline are reached within 0.5 – 1.5 hours after single oral administration of 0.451 mg levomefolate calcium. Steady state conditions for total folate in plasma after intake of 0.451 mg levomefolate calcium. In red blood cells, achievement of steady state is delayed due to the long lifespan of red blood cells of about 120 days. Levomefolate calcium is a part of contraceptive tablets: SAFYRA. Safyral is an estrogen/progestin COC (Combined Oral Contraceptive) containing a folate, indicated for use by women to: prevent pregnancy and raise folate levels in women who choose to use an oral contraceptive for contraception. COCs lower the risk of becoming pregnant primarily by suppressing ovulation. Other possible mechanisms may include cervical mucus changes that inhibit sperm penetration and endometrial changes that reduce the likelihood of implantation.

Approval Year

Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Preventing
SAFYRAL

Approved Use

1.1 Oral Contraceptive: Safyral is indicated for use by women to prevent pregnancy. 1.2 Folate Supplementation Safyral is indicated in women who choose to use an oral contraceptive as their method of contraception, to raise folate levels for the purpose of reducing the risk of a neural tube defect in a pregnancy conceived while taking the product or shortly after discontinuing the product.

Launch Date

2010
Sourcing

Sourcing

Vendor/AggregatorIDURL
PubMed

PubMed

TitleDatePubMed
Binding of radiolabeled folate and 5-methyltetrahydrofolate to cow's milk folate binding protein at pH 7.4 and 5.0. Relationship to concentration and polymerization equilibrium of the purified protein.
2001 Dec
Methylenetetrahydrofolate reductase polymorphism and susceptibility to breast cancer.
2002
Syntheses of labeled vitamers of folic acid to be used as internal standards in stable isotope dilution assays.
2002 Aug 14
Psychomotor retardation, spastic paraplegia, cerebellar ataxia and dyskinesia associated with low 5-methyltetrahydrofolate in cerebrospinal fluid: a novel neurometabolic condition responding to folinic acid substitution.
2002 Dec
Monitoring of methotrexate and reduced folates in the cerebrospinal fluid of cancer patients.
2002 Dec
Preponderance of methylenetetrahydrofolate reductase C677T homozygosity among leukemia patients intolerant to methotrexate.
2002 Dec
Distribution of plasma folate forms in hemodialysis patients receiving high daily doses of L-folinic or folic acid.
2002 Dec
Impaired NO-dependent vasodilation in patients with Type II (non-insulin-dependent) diabetes mellitus is restored by acute administration of folate.
2002 Jul
Nature and nurture in vitamin B12 deficiency.
2002 Jul
Antisense inhibition of methylenetetrahydrofolate reductase reduces survival of methionine-dependent tumour lines.
2002 Jul 15
Interaction of 5-methyltetrahydrofolate and tetrahydrobiopterin on endothelial function.
2002 Jun
Vitamin C therapy ameliorates vascular endothelial dysfunction in treated patients with homocystinuria.
2002 May
5-methyltetrahydrofolate restores endothelial function in uraemic patients on convective haemodialysis.
2002 May
Role of the C-terminus and the long cytoplasmic loop in reduced folate carrier expression and function.
2002 May 1
Effect of low doses of 5-methyltetrahydrofolate and folic acid on plasma homocysteine in healthy subjects with or without the 677C-->T polymorphism of methylenetetrahydrofolate reductase.
2002 Sep
Multiple transcription start sites and alternative splicing in the methylenetetrahydrofolate reductase gene result in two enzyme isoforms.
2002 Sep
Measurement of red blood cell methylfolate.
2002 Sep 28
Dietary prevention of post-angioplasty restenosis. From illusion and disillusion to pragmatism.
2003 Dec
Cobalamin-dependent methionine synthase: probing the role of the axial base in catalysis of methyl transfer between methyltetrahydrofolate and exogenous cob(I)alamin or cob(I)inamide.
2003 Dec 16
Transport of 5-formyltetrahydrofolate into primary cultured rat astrocytes.
2003 Feb 1
Determination of 5-methyltetrahydrofolic acid and folic acid in citrus juices using stable isotope dilution-mass spectrometry.
2003 Feb 26
Antisense modulation of the coding or regulatory sequence of the folate receptor (folate binding protein-1) in mouse embryos leads to neural tube defects.
2003 Jul
Characterization of mutations in severe methylenetetrahydrofolate reductase deficiency reveals an FAD-responsive mutation.
2003 May
Model studies on the stability of folic acid and 5-methyltetrahydrofolic acid degradation during thermal treatment in combination with high hydrostatic pressure.
2003 May 21
Folate improves endothelial function in patients with coronary heart disease.
2003 Nov
Hyperhomocystinemia in children with inflammatory bowel disease.
2003 Nov
Age dependence of the influence of methylenetetrahydrofolate reductase genotype on plasma homocysteine level.
2003 Nov 1
Thrombophilia and pregnancy.
2003 Nov 14
Characterization of a pseudogene for murine methylenetetrahydrofolate reductase.
2003 Oct
Regulation of S-adenosylmethionine levels in Saccharomyces cerevisiae.
2003 Oct 31
Hyperproliferation of homocysteine-treated colon cancer cells is reversed by folate and 5-methyltetrahydrofolate.
2004 Apr
The C677 mutation in methylene tetrahydrofolate reductase gene: correlation with uric acid and cardiovascular risk factors in elderly Korean men.
2004 Apr
Quantitative evaluation of the drug-drug interactions between methotrexate and nonsteroidal anti-inflammatory drugs in the renal uptake process based on the contribution of organic anion transporters and reduced folate carrier.
2004 Apr
A review of folate receptor alpha cycling and 5-methyltetrahydrofolate accumulation with an emphasis on cell models in vitro.
2004 Apr 29
Normal dopaminergic and serotonergic metabolites in cerebrospinal fluid and blood of restless legs syndrome patients.
2004 Feb
Folate, homocysteine, endothelial function and cardiovascular disease.
2004 Feb
Comparative study on pressure and temperature stability of 5-methyltetrahydrofolic acid in model systems and in food products.
2004 Feb 11
Methylenetetrahydrofolate reductase and transcobalamin genetic polymorphisms in human spontaneous abortion: biological and clinical implications.
2004 Feb 17
Red cell N5-methyltetrahydrofolate concentrations and C677T methylenetetrahydrofolate reductase genotype in patients with stroke.
2004 Jan
Thymidylate synthase and methylenetetrahydrofolate reductase gene polymorphisms: relationships with 5-fluorouracil sensitivity.
2004 Jan 26
Placental folate transport and binding are not impaired in pregnancies complicated by fetal growth restriction.
2004 Jul
Mutations of the MTHFR gene (428C>T and [458G>T+459C>T]) markedly decrease MTHFR enzyme activity.
2004 Jun
Pharmacokinetic study on the utilisation of 5-methyltetrahydrofolate and folic acid in patients with coronary artery disease.
2004 Mar
Sodium-dependent methotrexate carrier-1 is expressed in rat kidney: cloning and functional characterization.
2004 Mar
5-Methyltetrahydrofolic acid and folic acid measured in plasma with liquid chromatography tandem mass spectrometry: applications to folate absorption and metabolism.
2004 Mar 15
Homocysteine and reactive oxygen species in metabolic syndrome, type 2 diabetes mellitus, and atheroscleropathy: the pleiotropic effects of folate supplementation.
2004 May 10
The methionine synthase polymorphism D919G alters susceptibility to primary central nervous system lymphoma.
2004 May 17
Methionine metabolism in plants: chloroplasts are autonomous for de novo methionine synthesis and can import S-adenosylmethionine from the cytosol.
2004 May 21
Folic acid-mediated inhibition of serum-induced activation of EGFR promoter in colon cancer cells.
2004 Sep
Betaine rescue of an animal model with methylenetetrahydrofolate reductase deficiency.
2004 Sep 15
Patents

Sample Use Guides

Take one tablet daily by mouth at the same time every day
Route of Administration: Oral
neural stem cells (NSCs) were exposed to folic acid or 5-methyltetrahydrofolate (5-MTHF) (0-200 μmol/L) for 24, 48 or 72 h
Name Type Language
LEVOMEFOLATE SODIUM
Common Name English
L-GLUTAMIC ACID, N-(4-((((6S)-2-AMINO-3,4,5,6,7,8-HEXAHYDRO-5-METHYL-4-OXO-6-PTERIDINYL)METHYL)AMINO)BENZOYL)-, SODIUM SALT (1:2)
Systematic Name English
Code System Code Type Description
CAS
1423663-76-6
Created by admin on Sat Dec 16 10:09:12 GMT 2023 , Edited by admin on Sat Dec 16 10:09:12 GMT 2023
PRIMARY
PUBCHEM
135565435
Created by admin on Sat Dec 16 10:09:12 GMT 2023 , Edited by admin on Sat Dec 16 10:09:12 GMT 2023
PRIMARY
FDA UNII
B3KYL5163W
Created by admin on Sat Dec 16 10:09:12 GMT 2023 , Edited by admin on Sat Dec 16 10:09:12 GMT 2023
PRIMARY