Usage
L-methylfolate, the bioactive form of folate (vitamin B9), is primarily used to treat folate deficiency and conditions related to it, such as megaloblastic anemia. It is also used as adjunctive therapy in patients with major depressive disorder who have folate deficiency, or in those with schizophrenia and hyperhomocysteinemia related to folate deficiency. It supports the normal function of the immune system, normal blood formation, and reduces tiredness and fatigue. In women of childbearing age, it helps prevent neural tube defects in the developing fetus.
It’s pharmacological classification is vitamin.
L-methylfolate works by providing the body with the readily usable form of folate, bypassing the metabolic steps required for converting folic acid into its active form. This is particularly important for individuals with certain genetic variations (e.g., MTHFR gene mutations) affecting folate metabolism.
Alternate Names
- Levomefolic acid
- 5-Methyltetrahydrofolate (5-MTHF)
- 5-MTHF calcium salt
- (6S)-5-methyltetrahydrofolic acid
- (6S)-5-MTHF
Brand Names: Deplin, Denovo, Elfolate, L-Methylfolate Forte, XaQuil XR, L-Methylfolate Formula, Zervalx, Vilofane-DP, Duleek-DP, Deplin FC
How It Works
Pharmacodynamics: L-methylfolate is essential for various physiological processes, including DNA synthesis, cell division, and the production of red blood cells. It also plays a crucial role in the synthesis of neurotransmitters like serotonin, dopamine, and norepinephrine, influencing mood regulation and cognitive function. By lowering homocysteine levels, it contributes to cardiovascular health.
Pharmacokinetics: L-methylfolate is absorbed readily in the gastrointestinal tract, reaching peak plasma concentrations within approximately one hour. It is metabolized in the liver and excreted primarily through the kidneys.
Mode of Action: L-methylfolate acts as a cofactor for enzymes involved in one-carbon transfer reactions, including those necessary for DNA and RNA synthesis, amino acid metabolism, and methylation reactions. These reactions are vital for various cellular processes, growth, and development.
Receptor Binding/Enzyme Interactions: L-methylfolate does not directly bind to receptors but acts as a substrate and cofactor for key enzymes involved in folate metabolism. It participates in crucial metabolic cycles within the body, influencing the synthesis and function of various biomolecules.
Elimination: Primarily renal excretion.
Dosage
Standard Dosage
Adults:
- Folic Acid Deficiency: 7.5-15 mg orally once daily, with or without food. XaQuil XR: 30 mg orally once daily, with or without food.
- Adjunctive Treatment for Depression: 7.5-15 mg orally once daily.
- Megaloblastic Anemia: 7.5-15 mg orally once daily.
Children:
Dosing is weight and age-dependent and should be determined by a pediatrician. General guidelines include:
- Infants (0-6 months): 65 mcg/day
- Babies (7-12 months): 80 mcg/day
- Toddlers (1-3 years): 150 mcg/day
- Children (4-8 years): 200 mcg/day
- Pre-teens (9-13 years): 300 mcg/day
Safe upper limits:
- 1-3 years: 300 mcg/day
- 4-8 years: 400 mcg/day
- 9-13 years: 600 mcg/day
- 14-18 years: 800 mcg/day
Special Cases:
- Elderly Patients: No specific dosage adjustments are typically necessary, but it’s always wise to monitor for adverse effects.
- Patients with Renal Impairment: Data limited; exercise caution.
- Patients with Hepatic Dysfunction: Data limited; exercise caution.
- Patients with Comorbid Conditions: Monitor closely, especially in those with a history of bipolar disorder or vitamin B12 deficiency.
Clinical Use Cases
The dosage in clinical scenarios like intubation, surgical procedures, mechanical ventilation, ICU use, or emergency situations is not specifically different but may need adjustments based on the patient’s individual needs and the clinical context. It’s advisable to consult specialist literature and guidelines for these specific situations.
Dosage Adjustments
Dosages should be adjusted based on individual patient responses and clinical situations under the guidance of a healthcare professional. Factors to consider include renal/hepatic function, other medical conditions, concomitant medications, and patient tolerance.
Side Effects
Common Side Effects
Generally, L-methylfolate is well-tolerated. Common side effects are rare and may include:
- Upset stomach
- Loss of appetite
- Nausea
- Abdominal distension
- Gas (flatulence)
- Bitter or bad taste
- Altered sleep patterns
- Difficulty concentrating
- Irritability
Rare but Serious Side Effects
Allergic reactions such as rash, hives, swelling (especially of the face, lips, tongue, or throat), and difficulty breathing.
Long-Term Effects
Limited data exists on the long-term effects of high-dose L-methylfolate. Monitoring is recommended, especially concerning the potential masking of vitamin B12 deficiency.
Adverse Drug Reactions (ADR)
Serious ADRs are rare but can include severe allergic reactions requiring immediate medical intervention.
Contraindications
- Hypersensitivity to L-methylfolate or any ingredients in the formulation.
- Should not be used as monotherapy in pernicious or other megaloblastic anemias where Vitamin B12 deficiency is present.
Drug Interactions
L-methylfolate may interact with several medications, including:
- Anticonvulsants (e.g., phenytoin, phenobarbital, primidone, carbamazepine)
- Certain antibiotics (e.g., sulfasalazine)
- Cholesterol-lowering drugs (e.g., cholestyramine)
- Anti-cancer drugs (e.g., capecitabine, fluorouracil, methotrexate)
- Fluoxetine
- Isotretinoin
- Methylprednisolone
- Pancrelipase
- Pyrimethamine
- Triamterene
- Trimethoprim
- Warfarin
- Oral contraceptives
- Metformin
- NSAIDs
- Alcohol
Pregnancy and Breastfeeding
L-methylfolate is generally considered safe during pregnancy and breastfeeding, even essential during pregnancy for proper fetal development. However, high doses should only be taken under medical supervision. It’s crucial to discuss dosage and potential risks with a healthcare provider. Folate is excreted in breast milk, but the amounts are generally considered safe for nursing infants.
Drug Profile Summary
- Mechanism of Action: Provides readily usable folate for essential metabolic processes, including DNA synthesis, cell division, and neurotransmitter production.
- Side Effects: Generally well-tolerated, but rare side effects may include gastrointestinal issues and allergic reactions.
- Contraindications: Hypersensitivity, should not be used as monotherapy in B12 deficient megaloblastic anemia.
- Drug Interactions: Multiple potential drug interactions, including anticonvulsants, antibiotics, and certain other medications.
- Pregnancy & Breastfeeding: Generally considered safe and often recommended during pregnancy, but high doses require medical supervision.
- Dosage: Adult: 7.5-15mg/day for folate deficiency and adjunctive treatment for depression. Pediatric dosing is age and weight dependent.
- Monitoring Parameters: Folate levels, complete blood count, homocysteine levels (if applicable), and monitoring for adverse reactions.
Popular Combinations
L-methylfolate is often combined with other B vitamins, particularly methylcobalamin (vitamin B12) and pyridoxal 5-phosphate (vitamin B6), to address B vitamin deficiencies comprehensively and enhance their synergistic effects. Combining with DHA is specifically recommended for pregnant and breastfeeding women.
Precautions
- General Precautions: Assess for allergies and underlying medical conditions like B12 deficiency or bipolar disorder.
- Specific Populations: Monitor pregnant and breastfeeding women, children, and the elderly closely.
- Lifestyle Considerations: Excessive alcohol intake can interfere with folate absorption and metabolism.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for L-Methyl Folate?
A: The recommended dosage for adults with folate deficiency or as adjunctive treatment for depression is 7.5-15 mg orally once daily. Pediatric dosing is age and weight-dependent and requires consultation with a pediatrician.
Q2: Can L-Methyl Folate mask a Vitamin B12 deficiency?
A: Yes, high doses of L-methylfolate can potentially mask the hematological symptoms of vitamin B12 deficiency, while the neurological damage can continue to progress. It’s crucial to rule out B12 deficiency before initiating L-methylfolate therapy.
Q3: What is the difference between L-methylfolate and folic acid?
A: L-methylfolate is the biologically active form of folate, while folic acid is the synthetic form. L-methylfolate bypasses the metabolic conversion steps needed for folic acid activation, making it readily usable by the body.
Q4: Is L-methylfolate safe during pregnancy?
A: L-methylfolate is considered safe and even essential during pregnancy for neural tube development. Doses above the RDA (400mcg/day) should only be taken under medical supervision.
Q5: What are the signs and symptoms of L-methylfolate deficiency?
A: Fatigue, weakness, pallor, shortness of breath, headaches, palpitations, irritability, difficulty concentrating, and tingling or numbness in the extremities.
A: It is primarily metabolized in the liver and excreted via the kidneys.
Q7: Does L-methylfolate interact with any antidepressants?
A: While it can be used adjunctively with antidepressants, there’s a potential for interaction with certain SSRIs like fluoxetine. Monitor patients closely for adverse reactions.
Q8: Can L-methylfolate be used in children?
A: Yes, under the guidance of a pediatrician, but the dosage is lower than adult doses and needs to be carefully determined based on the child’s age, weight, and specific condition.
Q9: Are there any dietary sources of L-methylfolate?
A: Leafy green vegetables, legumes, citrus fruits, and fortified foods are natural sources of folate, which the body converts into L-methylfolate.
Q10: What should I do if I suspect an overdose of L-methylfolate?
A: Seek immediate medical attention or contact a poison control center.
This information is current as of February 16, 2025. Medical knowledge is constantly evolving, and it is essential to consult with a qualified healthcare professional for the most up-to-date information and personalized advice.
