U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS
This repository is under review for potential modification in compliance with Administration directives.

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

Molecular Formula C20H25N7O6
Molecular Weight 459.4558
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 2 / 2
E/Z Centers 0
Optical Activity UNSPECIFIED

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
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
57.7 nM
0.451 mg single, oral
dose: 0.451 mg
route of administration: Oral
experiment type: SINGLE
co-administered: ETHINYL ESTRADIOL
L-5-METHYLTETRAHYDROFOLATE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE
food status: FASTED
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
370 nM × h
0.451 mg single, oral
dose: 0.451 mg
route of administration: Oral
experiment type: SINGLE
co-administered: ETHINYL ESTRADIOL
L-5-METHYLTETRAHYDROFOLATE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE
food status: FASTED
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
5.5 h
0.451 mg single, oral
dose: 0.451 mg
route of administration: Oral
experiment type: SINGLE
co-administered: ETHINYL ESTRADIOL
L-5-METHYLTETRAHYDROFOLATE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE
food status: FASTED
Funbound

Funbound

ValueDoseCo-administeredAnalytePopulation
44%
0.451 mg single, oral
dose: 0.451 mg
route of administration: Oral
experiment type: SINGLE
co-administered: ETHINYL ESTRADIOL
L-5-METHYLTETRAHYDROFOLATE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE
food status: FASTED
Sourcing

Sourcing

Vendor/AggregatorIDURL
PubMed

PubMed

TitleDatePubMed
Methylenetetrahydrofolate reductase 677 C/T genotype and cardiovascular disease mortality in postmenopausal women.
2001 Apr 1
Marked suppression of the activity of some, but not all, antifolate compounds by augmentation of folate cofactor pools within tumor cells.
2001 Apr 1
Low seminal plasma folate concentrations are associated with low sperm density and count in male smokers and nonsmokers.
2001 Feb
Influence of a methionine synthase (D919G) polymorphism on plasma homocysteine and folate levels and relation to risk of myocardial infarction.
2001 Feb 15
Effect of food on the oral bioavailability of UFT and leucovorin in cancer patients.
2001 Mar
Enzymatic determination of homocysteine in cell extracts.
2001 Mar
Carrier-mediated transport of folic acid in BeWo cell monolayers as a model of the human trophoblast.
2001 Nov
Rapid method for the determination of total 5-methyltetrahydrofolate in blood by liquid chromatography with fluorescence detection.
2002 Jan 25
Determination of 5-methyltetrahydrofolate (13C-labeled and unlabeled) in human plasma and urine by combined liquid chromatography mass spectrometry.
2002 Jun 15
5-methyltetrahydrofolate restores endothelial function in uraemic patients on convective haemodialysis.
2002 May
Does the interaction between maternal folate intake and the methylenetetrahydrofolate reductase polymorphisms affect the risk of cleft lip with or without cleft palate?
2003 Apr 1
Reduced folate transport to the CNS in female Rett patients.
2003 Aug 26
Determination of 5-methyltetrahydrofolic acid and folic acid in citrus juices using stable isotope dilution-mass spectrometry.
2003 Feb 26
A method for the analysis of natural and synthetic folate in foods.
2003 Jan 15
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
Analysis of the human folate receptor beta gene for an association with neural tube defects.
2003 Jun
Residues 45 and 404 in the murine reduced folate carrier may interact to alter carrier binding and mobility.
2003 Jun 27
Specific and sensitive quantification of folate vitamers in foods by stable isotope dilution assays using high-performance liquid chromatography-tandem mass spectrometry.
2003 May
Characterization of a pseudogene for murine methylenetetrahydrofolate reductase.
2003 Oct
Regulation of S-adenosylmethionine levels in Saccharomyces cerevisiae.
2003 Oct 31
Cerebrospinal fluid pterins and folates in Aicardi-Goutières syndrome: a new phenotype.
2003 Sep 9
Hyperproliferation of homocysteine-treated colon cancer cells is reversed by folate and 5-methyltetrahydrofolate.
2004 Apr
A review of folate receptor alpha cycling and 5-methyltetrahydrofolate accumulation with an emphasis on cell models in vitro.
2004 Apr 29
Placental folate transport and binding are not impaired in pregnancies complicated by fetal growth restriction.
2004 Jul
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
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
Substance Class Chemical
Created
by admin
on Mon Mar 31 18:30:24 GMT 2025
Edited
by admin
on Mon Mar 31 18:30:24 GMT 2025
Record UNII
8S95DH25XC
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
L-METHYLFOLATE
VANDF  
Preferred Name English
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
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 Mon Mar 31 18:30:24 GMT 2025 , Edited by admin on Mon Mar 31 18:30:24 GMT 2025
PRIMARY
DRUG CENTRAL
4621
Created by admin on Mon Mar 31 18:30:24 GMT 2025 , Edited by admin on Mon Mar 31 18:30:24 GMT 2025
PRIMARY
WIKIPEDIA
LEVOMEFOLIC ACID
Created by admin on Mon Mar 31 18:30:24 GMT 2025 , Edited by admin on Mon Mar 31 18:30:24 GMT 2025
PRIMARY
PUBCHEM
135398561
Created by admin on Mon Mar 31 18:30:24 GMT 2025 , Edited by admin on Mon Mar 31 18:30:24 GMT 2025
PRIMARY
CAS
31690-09-2
Created by admin on Mon Mar 31 18:30:24 GMT 2025 , Edited by admin on Mon Mar 31 18:30:24 GMT 2025
PRIMARY
INN
8917
Created by admin on Mon Mar 31 18:30:24 GMT 2025 , Edited by admin on Mon Mar 31 18:30:24 GMT 2025
PRIMARY
DAILYMED
8S95DH25XC
Created by admin on Mon Mar 31 18:30:24 GMT 2025 , Edited by admin on Mon Mar 31 18:30:24 GMT 2025
PRIMARY
NCI_THESAURUS
C81119
Created by admin on Mon Mar 31 18:30:24 GMT 2025 , Edited by admin on Mon Mar 31 18:30:24 GMT 2025
PRIMARY
SMS_ID
100000127631
Created by admin on Mon Mar 31 18:30:24 GMT 2025 , Edited by admin on Mon Mar 31 18:30:24 GMT 2025
PRIMARY
DRUG BANK
DB11256
Created by admin on Mon Mar 31 18:30:24 GMT 2025 , Edited by admin on Mon Mar 31 18:30:24 GMT 2025
PRIMARY
EVMPD
SUB33688
Created by admin on Mon Mar 31 18:30:24 GMT 2025 , Edited by admin on Mon Mar 31 18:30:24 GMT 2025
PRIMARY
RXCUI
1025342
Created by admin on Mon Mar 31 18:30:24 GMT 2025 , Edited by admin on Mon Mar 31 18:30:24 GMT 2025
PRIMARY
CHEBI
18608
Created by admin on Mon Mar 31 18:30:24 GMT 2025 , Edited by admin on Mon Mar 31 18:30:24 GMT 2025
PRIMARY
EPA CompTox
DTXSID00185583
Created by admin on Mon Mar 31 18:30:24 GMT 2025 , Edited by admin on Mon Mar 31 18:30:24 GMT 2025
PRIMARY
RXCUI
1592257
Created by admin on Mon Mar 31 18:30:24 GMT 2025 , Edited by admin on Mon Mar 31 18:30:24 GMT 2025
ALTERNATIVE
NCI_THESAURUS
C1505
Created by admin on Mon Mar 31 18:30:24 GMT 2025 , Edited by admin on Mon Mar 31 18:30:24 GMT 2025
CONCEPT Dietary Supplement
USAN
TT-129
Created by admin on Mon Mar 31 18:30:24 GMT 2025 , Edited by admin on Mon Mar 31 18:30:24 GMT 2025
PRIMARY
ChEMBL
CHEMBL1231574
Created by admin on Mon Mar 31 18:30:24 GMT 2025 , Edited by admin on Mon Mar 31 18:30:24 GMT 2025
PRIMARY
Related Record Type Details
SALT/SOLVATE -> PARENT
SALT/SOLVATE -> PARENT
SALT/SOLVATE -> PARENT
SALT/SOLVATE -> PARENT
SALT/SOLVATE -> PARENT
SALT/SOLVATE -> PARENT
SALT/SOLVATE -> PARENT
SALT/SOLVATE -> PARENT
SALT/SOLVATE -> PARENT
SALT/SOLVATE -> PARENT
Related Record Type Details
PARENT -> METABOLITE
Related Record Type Details
ACTIVE MOIETY