methylfolate
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
Earliest trial started May 1, 2005 (NCT00372645)
Timeline
Indications
Studied for
- Anxiety Disorders · Phase 4
- Attention Deficit Disorder with Hyperactivity · Phase 2/Phase 3
- Blood · Phase 2
- Brain Injuries · Phase 1/Phase 2
- Contraception · Phase 1
- Depression · Phase 4
- Diarrhea · Phase 4
- Hypertension, Renal · Phase 4
- Kidney Failure, Chronic · Phase 4
- Multiple Sclerosis · Phase 1
- Ovulation Inhibition · Phase 1
Mechanism of action
- Serotonin receptor (2b and 2c)BINDING AGENT
Serotonin receptor (2b and 2c) binding agent
- Unspecified targetOTHER
Unknown
Chemistry & pharmacology
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
- ChEMBLCHEMBL1231574 ↗
- WikipediaLevomefolic acid ↗
- NCATS8S95DH25XC ↗
- ChEMBLCHEMBL1615371 ↗
- NCATSA9R10K3F2F ↗
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 ID | Phase | Start date | Sponsor(s) |
|---|---|---|---|
| NCT06758778 | N/A | Jan 3, 2025 | SICHUAN CREDIT PHARMACEUTICAL CO., LTD. |
| NCT06218030 | Phase 4 | Apr 30, 2024 | Queen's University, Belfast |
| NCT05807711 | Phase 4 | Apr 1, 2023 | Alexandria University |
| NCT05931965 | N/A | Oct 5, 2022 | Riphah International University |
| NCT04782037 | Phase 4 | Oct 21, 2020 | King Edward Medical University, Mayo Hospital, Pakistan |
| NCT04095052 | N/A | Aug 14, 2019 | Oklahoma State University |
| NCT02696512 | Phase 1/Phase 2 (Phase 2) | Mar 1, 2016 | International Brain Research Foundation |
| NCT02133898 | N/A | Feb 29, 2016 | Pamlab, University of Florida |
| NCT01853280 | Phase 2/Phase 3 (Phase 3) | May 1, 2014 | Harvard University, Pamlab |
| NCT01584050 | N/A | May 1, 2012 | University of British Columbia |
| NCT01570088 | Phase 2 | Apr 1, 2012 | University of British Columbia |
| NCT01503892 | N/A | Dec 1, 2011 | Goldfarb Foundation, Pamlab, Temple University |
| NCT01381354 | Phase 1 | Oct 1, 2010 | DJO Incorporated, Pinnaclife Inc., TZ Press, LLC, University of Iowa |
| NCT01091506 | N/A | Mar 31, 2010 | Harvard University, Pamlab |
| NCT01031355 | Phase 1 | Dec 1, 2009 | Bayer |
| NCT00955955 | Phase 4 | Jul 31, 2009 | Harvard University, Pamlab |
| NCT01258660 | Phase 1 | Dec 1, 2006 | Bayer |
| NCT00853879 | N/A | Dec 1, 2006 | Northwell Health |
| NCT01253187 | Phase 1 | Oct 1, 2006 | Bayer |
| NCT01253174 | Phase 1 | Aug 1, 2006 | Bayer |
Organizations
Research & Development (27)
| Organization | Org type | Trials | As lead sponsor | Phases | Earliest year |
|---|---|---|---|---|---|
| Pamlab | For profit | 5 | 1 | 3 | 2009 |
| Bayer | For profit | 4 | 4 | 1 | 2006 |
| Harvard University | Academic/Hospital | 4 | 2 | 3 | 2006 |
| University of British Columbia | Academic/Hospital | 2 | 2 | 2 | 2012 |
| Alexandria University | Academic/Hospital | 1 | 1 | 1 | 2023 |
| Baylor University | Academic/Hospital | 1 | 0 | 1 | 2006 |
| DJO Incorporated | For profit | 1 | 0 | 1 | 2010 |
| Food Standards Agency, United Kingdom | Government | 1 | 0 | 1 | 2005 |
| Goldfarb Foundation | Academic/Hospital | 1 | 0 | 1 | 2011 |
| Greenwood Genetic Center | Academic/Hospital | 1 | 0 | 1 | 2006 |
| International Brain Research Foundation | Academic/Hospital | 1 | 1 | 1 | 2016 |
| King Edward Medical University | Academic/Hospital | 1 | 1 | 1 | 2020 |
| Mayo Hospital, Pakistan | Academic/Hospital | 1 | 0 | 1 | 2020 |
| National Institutes of Health (NIH) | Government | 1 | 0 | 1 | 2006 |
| Northwell Health | Academic/Hospital | 1 | 1 | 1 | 2006 |
| Oklahoma State University | Academic/Hospital | 1 | 1 | 1 | 2019 |
| Pinnaclife Inc. | For profit | 1 | 0 | 1 | 2010 |
| Quadram Institute | Academic/Hospital | 1 | 1 | 1 | 2005 |
| Queen's University, Belfast | Academic/Hospital | 1 | 1 | 1 | 2024 |
| Riphah International University | Academic/Hospital | 1 | 1 | 1 | 2022 |