methylfolate

Small moleculeexperimental

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. — NCATS

Clinical trial activity

22 trials · 27 clinical orgs · 0 marketing orgs

Phase 1
6
Phase 2
2
Phase 3
1
Phase 4
4

Earliest trial started May 1, 2005 (NCT00372645)

Timeline

2000s

  1. Jan 1, 2006

    Earliest Phase 1 Sponsor(trial)

2010s

  1. Jan 1, 2012

    Earliest Phase 2 Sponsor(trial)

Indications

Mechanism of action

Chemistry & pharmacology

Loading structure…

SMILES

CN1c2c([nH]c(N)nc2=O)NC[C@@H]1CNc1ccc(C(=O)N[C@@H](CCC(=O)O)C(=O)O)cc1
Mol. weight
459.46 g/mol
Lipinski Ro5
1 violation(s)
Rule of 3
No
Chirality
Single Stereoisomer
Inorganic
No
Polymer
No
Delivery
Oral
Availability
Prescription Only

Oral

Yes

Parenteral

No

Topical

No

Sources

Also known as

  • (6s)-5-methyltetrahydrofolate
  • (6s)-5-methyltetrahydrofolate
  • (6s)-5-methyltetrahydrofolic acid
  • (6s)-5-methyltetrahydrofolic acid
  • (6s)-5-mthf
  • (6s)-5-mthf
  • bodyfolin
  • bodyfolin
  • l-5-methyltetrahydrofolate
  • l-5-methyltetrahydrofolate
  • l-5-mthf
  • l-5-mthf
  • l-5-mthf
  • levomefolate
  • levomefolate
  • levomefolate calcium
  • levomefolate calcium
  • levomefolate calcium
  • levomefolate calcium
  • levomefolate calcium
  • levomefolate magnesium
  • levomefolate magnesium
  • levomefolate magnesium
  • levomefolate magnesium
  • levomefolic acid
  • levomefolic acid
  • levomefolic acid
  • levomefolic acid
  • levomefolic acid
  • lmca
  • lmca
  • l-methylfolate
  • l-methylfolate
  • l-methylfolate
  • l-methyl folate
  • lmsr
  • lmsr
  • lmsr
  • mefolinate
  • metafolin
  • metafolin
  • metafolin
  • metafolin
  • metafolin
  • methylfolate
  • methylfolate
  • methylfolate
  • methyl folate
  • methyl folate
  • methyl folate
  • n-(4-(((2-amino-1,4,5,6,7,8-hexahydro-5-methyl-4-oxo-6-pteridinyl)methyl)amino)benzoyl)-l-glutamic acid calcium salt
  • n-[4-[[[(6s)-2-amino-3,4,5,6,7,8-hexahydro-5-methyl-4-oxo-6-pteridinyl]methyl]amino]benzoyl]-l-glutamic acid
  • n-[4-[[[(6s)-2-amino-3,4,5,6,7,8-hexahydro-5-methyl-4-oxo-6-pteridinyl]methyl]amino]benzoyl]-l-glutamic acid
  • nutrifolin
  • nutrifolin
  • safyral

Clinical trials

NCT IDPhaseStart dateSponsor(s)
NCT06758778N/AJan 3, 2025SICHUAN CREDIT PHARMACEUTICAL CO., LTD.
NCT06218030Phase 4Apr 30, 2024Queen's University, Belfast
NCT05807711Phase 4Apr 1, 2023Alexandria University
NCT05931965N/AOct 5, 2022Riphah International University
NCT04782037Phase 4Oct 21, 2020King Edward Medical University, Mayo Hospital, Pakistan
NCT04095052N/AAug 14, 2019Oklahoma State University
NCT02696512Phase 1/Phase 2 (Phase 2)Mar 1, 2016International Brain Research Foundation
NCT02133898N/AFeb 29, 2016Pamlab, University of Florida
NCT01853280Phase 2/Phase 3 (Phase 3)May 1, 2014Harvard University, Pamlab
NCT01584050N/AMay 1, 2012University of British Columbia
NCT01570088Phase 2Apr 1, 2012University of British Columbia
NCT01503892N/ADec 1, 2011Goldfarb Foundation, Pamlab, Temple University
NCT01381354Phase 1Oct 1, 2010DJO Incorporated, Pinnaclife Inc., TZ Press, LLC, University of Iowa
NCT01091506N/AMar 31, 2010Harvard University, Pamlab
NCT01031355Phase 1Dec 1, 2009Bayer
NCT00955955Phase 4Jul 31, 2009Harvard University, Pamlab
NCT01258660Phase 1Dec 1, 2006Bayer
NCT00853879N/ADec 1, 2006Northwell Health
NCT01253187Phase 1Oct 1, 2006Bayer
NCT01253174Phase 1Aug 1, 2006Bayer
Showing 20 of 22 trials
Page 1 / 2

Organizations

Research & Development (27)

OrganizationOrg typeTrialsAs lead sponsorPhasesEarliest year
PamlabFor profit5132009
BayerFor profit4412006
Harvard UniversityAcademic/Hospital4232006
University of British ColumbiaAcademic/Hospital2222012
Alexandria UniversityAcademic/Hospital1112023
Baylor UniversityAcademic/Hospital1012006
DJO IncorporatedFor profit1012010
Food Standards Agency, United KingdomGovernment1012005
Goldfarb FoundationAcademic/Hospital1012011
Greenwood Genetic CenterAcademic/Hospital1012006
International Brain Research FoundationAcademic/Hospital1112016
King Edward Medical UniversityAcademic/Hospital1112020
Mayo Hospital, PakistanAcademic/Hospital1012020
National Institutes of Health (NIH)Government1012006
Northwell HealthAcademic/Hospital1112006
Oklahoma State UniversityAcademic/Hospital1112019
Pinnaclife Inc.For profit1012010
Quadram InstituteAcademic/Hospital1112005
Queen's University, BelfastAcademic/Hospital1112024
Riphah International UniversityAcademic/Hospital1112022
27 organizations
Page 1 / 2