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

Details

Stereochemistry ABSOLUTE
Molecular Formula C20H25N7O6
Molecular Weight 459.4558
Optical Activity UNSPECIFIED
Defined Stereocenters 2 / 2
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of LEVOMEFOLIC ACID

SMILES

CN1[C@@H](CNC2=CC=C(C=C2)C(=O)N[C@@H](CCC(O)=O)C(O)=O)CNC3=C1C(=O)NC(N)=N3

InChI

InChIKey=ZNOVTXRBGFNYRX-STQMWFEESA-N
InChI=1S/C20H25N7O6/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)/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

1.29237123E12
Sourcing

Sourcing

Vendor/AggregatorIDURL
PubMed

PubMed

TitleDatePubMed
Serum folate levels after UVA exposure: a two-group parallel randomised controlled trial.
2001
Determination of folates in foods by high-performance liquid chromatography with fluorescence detection after precolumn conversion to 5-methyltetrahydrofolates.
2001 Aug 31
Association of methylenetetrahydrofolate reductase polymorphism C677T and dietary folate with the risk of cervical dysplasia.
2001 Dec
Folate protects against oxidative modification of human LDL.
2001 Dec
Assays of methylenetetrahydrofolate reductase and methionine synthase activities by monitoring 5-methyltetrahydrofolate and tetrahydrofolate using high-performance liquid chromatography with fluorescence detection.
2001 Dec 15
Carrier-mediated transport of folic acid in BeWo cell monolayers as a model of the human trophoblast.
2001 Nov
Plasma folate, vitamin B(12), and total homocysteine and homozygosity for the C677T mutation of the 5,10-methylene tetrahydrofolate reductase gene in patients with Alzheimer's dementia. A case-control study.
2001 Nov-Dec
Treatment of hyperhomocysteinemia in end-stage renal disease.
2001 Oct
High-performance liquid chromatographic measurement of 5,10-methylenetetrahydrofolate in liver.
2001 Oct 15
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
Downregulation of reduced-folate transporter by glucose in cultured RPE cells and in RPE of diabetic mice.
2002 Feb
Folic acid improves endothelial function in coronary artery disease via mechanisms largely independent of homocysteine lowering.
2002 Jan 1
Rapid method for the determination of total 5-methyltetrahydrofolate in blood by liquid chromatography with fluorescence detection.
2002 Jan 25
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
5,10-Methylenetetrahydrofolate reductase (MTHFR) assay in the forward direction: residual activity in MTHFR deficiency.
2002 Jun
The C677T mutation in the methylenetetrahydrofolate reductase gene contributes to hyperhomocysteinemia in patients taking anticonvulsants.
2002 Jun
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
Role of the C-terminus and the long cytoplasmic loop in reduced folate carrier expression and function.
2002 May 1
Cytoplasmic serine hydroxymethyltransferase mediates competition between folate-dependent deoxyribonucleotide and S-adenosylmethionine biosyntheses.
2002 Oct 11
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
The enrichment of eggs with folic acid through supplementation of the laying hen diet.
2002 Sep
Intimal redox stress: accelerated atherosclerosis in metabolic syndrome and type 2 diabetes mellitus. Atheroscleropathy.
2002 Sep 27
Measurement of red blood cell methylfolate.
2002 Sep 28
Uptake of 5-methyltetrahydrofolate into PC-3 human prostate cancer cells is carrier-mediated.
2003 Aug
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
Determination of 5-methyltetrahydrofolic acid and folic acid in citrus juices using stable isotope dilution-mass spectrometry.
2003 Feb 26
A comparison of folic acid and 5-methyltetrahydrofolate for prevention of DNA damage and cell death in human lymphocytes in vitro.
2003 Jan
Analysis of the human folate receptor beta gene for an association with neural tube defects.
2003 Jun
A mass spectrometric validated high-performance liquid chromatography procedure for the determination of folates in foods.
2003 Jun 18
Residues 45 and 404 in the murine reduced folate carrier may interact to alter carrier binding and mobility.
2003 Jun 27
Hyperhomocystinemia in children with inflammatory bowel disease.
2003 Nov
Regulation of S-adenosylmethionine levels in Saccharomyces cerevisiae.
2003 Oct 31
The C677 mutation in methylene tetrahydrofolate reductase gene: correlation with uric acid and cardiovascular risk factors in elderly Korean men.
2004 Apr
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
Determination of folate vitamers in human serum by stable-isotope-dilution tandem mass spectrometry and comparison with radioassay and microbiologic assay.
2004 Feb
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
Folic acid rescues nitric oxide-induced neural tube closure defects.
2004 Mar
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
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
LEVOMEFOLIC ACID
INN   USAN   WHO-DD  
INN   USAN  
Official Name English
N-(4-((((6S)-2-AMINO-5-METHYL-4-OXO-1,4,5,6,7,8-HEXAHYDROPTERIDIN-6- YL)METHYL)AMINO)BENZOYL)-L-GLUTAMIC ACID
Systematic Name English
L-5-MTHF
Common Name English
(6S)-5-methyltetrahydrofolate [WHO-DD]
Common Name English
(6S)-5-METHYLTETRAHYDROFOLATE
WHO-DD  
Common Name English
L-METHYLFOLATE
VANDF  
Common Name English
5- METHYLTETRAHYDROFOLATE
Common Name English
5-METHYL-(6S)-TETRAHYDROFOLIC ACID
Common Name English
LEVOMEFOLATE
VANDF  
Common Name English
Levomefolic acid [WHO-DD]
Common Name English
levomefolic acid [INN]
Common Name English
LEVOMEFOLATE [VANDF]
Common Name English
5-MTHF
Common Name English
LEVOMEFOLINIC ACID
Common Name English
L-METHYLFOLATE [VANDF]
Common Name English
LMSR
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)-
Common Name English
LEVOMEFOLIC ACID [USAN]
Common Name English
Code System Code Type Description
FDA UNII
8S95DH25XC
Created by admin on Wed Jul 05 23:57:11 UTC 2023 , Edited by admin on Wed Jul 05 23:57:11 UTC 2023
PRIMARY
DRUG CENTRAL
4621
Created by admin on Wed Jul 05 23:57:11 UTC 2023 , Edited by admin on Wed Jul 05 23:57:11 UTC 2023
PRIMARY
WIKIPEDIA
LEVOMEFOLIC ACID
Created by admin on Wed Jul 05 23:57:11 UTC 2023 , Edited by admin on Wed Jul 05 23:57:11 UTC 2023
PRIMARY
PUBCHEM
135398561
Created by admin on Wed Jul 05 23:57:11 UTC 2023 , Edited by admin on Wed Jul 05 23:57:11 UTC 2023
PRIMARY
CAS
31690-09-2
Created by admin on Wed Jul 05 23:57:11 UTC 2023 , Edited by admin on Wed Jul 05 23:57:11 UTC 2023
PRIMARY
INN
8917
Created by admin on Wed Jul 05 23:57:11 UTC 2023 , Edited by admin on Wed Jul 05 23:57:11 UTC 2023
PRIMARY
DAILYMED
8S95DH25XC
Created by admin on Wed Jul 05 23:57:11 UTC 2023 , Edited by admin on Wed Jul 05 23:57:11 UTC 2023
PRIMARY
NCI_THESAURUS
C81119
Created by admin on Wed Jul 05 23:57:11 UTC 2023 , Edited by admin on Wed Jul 05 23:57:11 UTC 2023
PRIMARY
SMS_ID
100000127631
Created by admin on Wed Jul 05 23:57:11 UTC 2023 , Edited by admin on Wed Jul 05 23:57:11 UTC 2023
PRIMARY
DRUG BANK
DB11256
Created by admin on Wed Jul 05 23:57:11 UTC 2023 , Edited by admin on Wed Jul 05 23:57:11 UTC 2023
PRIMARY
EVMPD
SUB33688
Created by admin on Wed Jul 05 23:57:11 UTC 2023 , Edited by admin on Wed Jul 05 23:57:11 UTC 2023
PRIMARY
RXCUI
1025342
Created by admin on Wed Jul 05 23:57:11 UTC 2023 , Edited by admin on Wed Jul 05 23:57:11 UTC 2023
PRIMARY
CHEBI
18608
Created by admin on Wed Jul 05 23:57:11 UTC 2023 , Edited by admin on Wed Jul 05 23:57:11 UTC 2023
PRIMARY
EPA CompTox
DTXSID00185583
Created by admin on Wed Jul 05 23:57:11 UTC 2023 , Edited by admin on Wed Jul 05 23:57:11 UTC 2023
PRIMARY
RXCUI
1592257
Created by admin on Wed Jul 05 23:57:11 UTC 2023 , Edited by admin on Wed Jul 05 23:57:11 UTC 2023
ALTERNATIVE
NCI_THESAURUS
C1505
Created by admin on Wed Jul 05 23:57:11 UTC 2023 , Edited by admin on Wed Jul 05 23:57:11 UTC 2023
CONCEPT Dietary Supplement
USAN
TT-129
Created by admin on Wed Jul 05 23:57:11 UTC 2023 , Edited by admin on Wed Jul 05 23:57:11 UTC 2023
PRIMARY
ChEMBL
CHEMBL1231574
Created by admin on Wed Jul 05 23:57:11 UTC 2023 , Edited by admin on Wed Jul 05 23:57:11 UTC 2023
PRIMARY