Levomefolic acid

Quality 0.50 · 2 views · Updated 2 months ago

title: "Levomefolic acid" type: doc version: 1 created: 2026-02-28 author: "Wikipedia contributors" status: active scope: public tags: ["folates", "coenzymes", "medical-food", "patent-case-law"] topic_path: "law" source: "https://en.wikipedia.org/wiki/Levomefolic_acid" license: "CC BY-SA 4.0" wikipedia_page_id: 0 wikipedia_revision_id: 0

| ImageFile=5-Methyltetrahydrofolate.png | ImageClass = skin-invert-image | ImageSize=220px | IUPACName=(2S)-2-[ [4-[(2-Amino-5-methyl-4-oxo-1,6,7,8-tetrahydropteridin-6-yl) methylamino]benzoyl]amino]pentanedioic acid | OtherNames=(L-5-Me-THFA, L-5-Me-H4FA), anion: L-5-methyltetrahydrofolate (L-5-Me-THF, L-5-Me-H4F), L-methylfolate Metafolin |Section1={{Chembox Identifiers | UNII_Ref = | UNII = 8S95DH25XC | UNII1_Ref = | UNII1 = A9R10K3F2F | UNII1_Comment = (calcium salt) | ChemSpiderID = 392351 | ChEBI = 136009 | SMILES = CN1c2c([nH]c(nc2=O)N)NC[C@@H]1CNc3ccc(cc3)C(=O)NC@@HC(=O)O | InChI = 1/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 | InChIKey = ZNOVTXRBGFNYRX-STQMWFEEBP | StdInChI = 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 | StdInChIKey = ZNOVTXRBGFNYRX-STQMWFEESA-N | CASNo= 31690-09-2 | CASNo1 = 151533-22-1 | CASNo1_Comment = (calcium salt) | PubChem=444412 | PubChem1 = 15341110 | PubChem1_Comment = (calcium salt) | KEGG = D09353 | MeSHName=5-methyltetrahydrofolate

|Section2={{Chembox Properties | C=20 | H=25 | N=7 | O=6 | Appearance= | Density= | MeltingPt= | BoilingPt= | Solubility= |Section7={{Chembox Hazards | MainHazards= | FlashPt= | AutoignitionPt = |Section6={{Chembox Pharmacology | ATCCode_prefix = B03 | ATCCode_suffix = BB51 | AdminRoutes = oral, transdermal, subcutaneous | Bioavail = | Metabolism = | HalfLife = | ProteinBound = | Excretion = | Legal_status = | Legal_US = OTC | Legal_US_comment = | Legal_UK = | Legal_AU = | Legal_CA = | Pregnancy_category= | Pregnancy_AU =

Levomefolic acid (INN, also known as L-5-MTHF, L-methylfolate and L-5-methyltetrahydrofolate and (6S)-5-methyltetrahydrofolate, and (6S)-5-MTHF) is the primary biologically active form of folate used at the cellular level for DNA reproduction, the cysteine cycle and the regulation of homocysteine. It is also the form found in circulation and transported across membranes into tissues and across the blood–brain barrier. In the cell, L-methylfolate is used in the methylation of homocysteine to form methionine and tetrahydrofolate (THF). THF is the immediate acceptor of one carbon unit for the synthesis of thymidine-DNA, purines (RNA and DNA) and methionine. The un-methylated form, folic acid (vitamin B9), is a synthetic form of folate, and must undergo enzymatic reduction by dihydrofolate reductase (DHFR) to become biologically active. Systematic reviews suggest that adjunctive L-methylfolate modestly improves symptoms in major depressive disorder.

It is synthesized in the absorptive cells of the small intestine from polyglutamylated dietary folate. It is a methylated derivative of tetrahydrofolate. Levomefolic acid is generated by methylenetetrahydrofolate reductase (MTHFR) from 5,10-methylenetetrahydrofolate (MTHF) and used to recycle homocysteine back to methionine by methionine synthase (MS).

L-methylfolate is water-soluble and primarily excreted via the kidneys. In a study of 21 subjects with coronary artery disease, peak plasma levels were reached in one to three hours following oral or parenteral administration. Peak concentrations were found to be more than seven times higher than folic acid (129 ng/ml vs. 14.1 ng/ml).

Patients at risk for vitamin B12 deficiency should consult with their medical provider prior to taking L-Methylfolate. The interrelationship between these two vitamins (L-Methylfolate and B12) is best explained by the methyl trap hypothesis.

Metabolism

::figure[src="https://upload.wikimedia.org/wikipedia/commons/d/d5/MTHFR_metabolism.svg" caption="THF]]: tetrahydrofolate."] ::

Medical uses

Major depressive disorder and other psychiatric conditions

Systematic reviews suggest that adjunctive L-methylfolate modestly improves symptoms in major depressive disorder and may benefit other psychiatric conditions with good tolerability. In patients with depression augmenting SSRI/SNRI treatment, L-methylfolate augmentation led to higher medication adherence and lower health care utilization and costs compared to augmentation with second-generation atypical antipsychotics.

Cardiovascular disease and cancer

Levomefolic acid (and folic acid in turn) has been proposed for treatment of cardiovascular disease and advanced cancers such as breast and colorectal cancers. It bypasses several metabolic steps in the body and better binds thymidylate synthase with FdUMP, a metabolite of the drug fluorouracil.

Patent issues

In March 2012, Merck & Cie of Switzerland, Pamlab LLC (maker of Metanx and Cerefolin, Neevo DHA, and Deplin), and South Alabama Medical Science Foundation (SAMSF) (the plaintiffs) filed a complaint in the United States District Court for the Eastern District of Texas against four defendants: Macoven Pharmaceuticals (owned by Pernix Therapeutics), Gnosis SpA of Italy, Gnosis U.S.A and Gnosis Bioresearch Switzerland. The plaintiffs alleged that the defendants infringed on several of the plaintiffs' patents. The Macoven products named in the suit are: "Vitaciric-B", "ALZ-NAC", "PNV DHA", and l-methylfolate calcium (levomefolate calcium).

In September 2012, the same three plaintiffs filed a complaint requesting that the International Trade Commission begin a investigation of the same four defendants. The complaint states that Gnosis' "Extrafolic-S" and products which are made from it, infringe upon three of their patents: , , and .

Formulations

  • Levomefolate calcium, a calcium salt of levomefolic acid is sold under the brand name Metafolin and incorporated in Deplin.
  • Levomefolate magnesium is a magnesium salt of levomefolic acid, manufactured as DeltaFolate, a primary ingredient in EnLyte.
  • Levomefolate calcium (a calcium salt of levomefolic acid) is manufactured as Cerebrofolate.

References

References

  1. (August 2010). "Folic acid and L-5-methyltetrahydrofolate: comparison of clinical pharmacokinetics and pharmacodynamics". Clinical Pharmacokinetics.
  2. "5-methyltetrahydrofolate – Compound Summary". NCBI.
  3. "CerefolinNAC Caplets Package Insert".
  4. (1985). "Vitamin B12-folate interrelationships". Annual Review of Nutrition.
  5. (2006). "Cellular folate vitamer distribution during and after correction of vitamin B12 deficiency: a case for the methylfolate trap". British Journal of Haematology.
  6. (2022). "Systematic Review and Meta-Analysis of L-Methylfolate Augmentation in Depressive Disorders". Pharmacopsychiatry.
  7. (2022). "The potential use of folate and its derivatives in treating psychiatric disorders: A systematic review". Biomedicine & Pharmacotherapy.
  8. (January 2014). "Comparative assessment of adherence measures and resource use in SSRI/SNRI-treated patients with depression using second-generation antipsychotics or L-methylfolate as adjunctive therapy". Journal of Managed Care Pharmacy.
  9. (March 2004). "Pharmacokinetic study on the utilisation of 5-methyltetrahydrofolate and folic acid in patients with coronary artery disease". Nature Publishing Group.
  10. (June 2005). "Folic acid and colorectal cancer prevention: molecular mechanisms and epidemiological evidence (Review)". International Journal of Oncology.
  11. The six patents named were {{patent. US. 5997915, {{patent. US. 6011040, {{patent. US. 6254904, {{patent. US. 6673381, {{patent. US. 7674490 and {{patent. US. 7172778.
  12. (6 March 2012). "Pernix Therapeutics' Subsidiary Macoven Pharmaceuticals, LLC Named in Suit by Merck, Pamlab, L.L.C. and Others for Alleged". Bloomberg.
  13. Schweibenz, Eric W.. (2012-09-10). "SAMSF, Merck, and Pamlab File New 337 Complaint Regarding Certain Reduced Folate Nutraceutical Products and L-methylfolate Raw Ingredients Used Therein". Oblon, Spivak, McClelland, Maier & Neustadt, L.L.P..
  14. "Metafolin".
  15. "DEPLIN®".
  16. "EnLyte with DeltaFolate".
  17. "COMPARATIVE IN VITRO EVALUATION OF (6S)-5- METHYLTETRAHYDROFOLATE BRANDS: THE POST MARKET SURVEILLANCE FOR QUALITY ASSESSMENT".

::callout[type=info title="Wikipedia Source"] This article was imported from Wikipedia and is available under the Creative Commons Attribution-ShareAlike 4.0 License. Content has been adapted to SurfDoc format. Original contributors can be found on the article history page. ::

folatescoenzymesmedical-foodpatent-case-law