Introduction
Calcium L-5-Methyltetrahydrofolate (L-5-MTHF-Ca), also known as calcium L-methylfolate or levomefolate calcium, is the biologically active calcium salt form of folate (Vitamin B9). It is the predominant naturally circulating form of folate in the human body and can be directly utilized by cells without the need for enzymatic reduction.
Unlike conventional folic acid-a synthetic form that requires multi-step enzymatic conversion via dihydrofolate reductase (DHFR) and methylenetetrahydrofolate reductase (MTHFR)-L-5-MTHF-Ca bypasses these metabolic steps entirely. This direct bioavailability is especially critical for the estimated 30–60% of the global population carrying MTHFR gene polymorphisms that impair folic acid metabolism.
L-5-MTHF-Ca plays essential roles in one-carbon metabolism, DNA synthesis and repair, homocysteine remethylation to methionine, and neurotransmitter biosynthesis. As a highly pure, stabilized calcium salt, our product offers superior stability compared to free acid forms and is the preferred folate source for premium dietary supplements, infant formulas, medical foods, and functional nutrition products worldwide.
Product Forms & Specifications
| Parameter | Specification | Method |
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| Assay (L-5-MTHF-Ca, anhydrous basis) | 95.0%–102.0% | HPLC |
| Appearance | Off-white to light yellowish powder | Visual |
| Identification | Positive (IR / HPLC) | IR / HPLC |
| Water Content | ≤ 8.0% | Karl Fischer |
| pH (1% aqueous suspension) | 6.0–7.5 | pH Meter |
| L-5-MTHF Isomer Purity | ≥ 99.0% | Chiral HPLC |
| Related Substances (Total) | ≤ 2.0% | HPLC |
| Calcium Content | 7.0%–8.5% (anhydrous basis) | Complexometric Titration |
Calcium L-5-Methyltetrahydrofolate Benefits
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Superior Bioavailability - Directly Active FormL-5-MTHF-Ca is the metabolically active folate form that requires no enzymatic conversion. Clinical pharmacokinetic studies demonstrate that orally administered L-5-MTHF-Ca achieves significantly higher and faster peak plasma folate concentrations compared to equimolar doses of folic acid, especially in individuals with reduced MTHFR enzyme activity. |
Effective Homocysteine ReductionAs the methyl donor in the remethylation of homocysteine to methionine, L-5-MTHF-Ca directly participates in maintaining healthy plasma homocysteine levels. Randomized controlled trials have demonstrated that low-dose L-5-MTHF supplementation effectively reduces plasma homocysteine concentrations, an independent risk factor for cardiovascular, cerebrovascular, and neurodegenerative conditions. |
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Mental Health & Cognitive SupportL-5-MTHF-Ca crosses the blood-brain barrier and serves as the sole methyl donor for the synthesis of serotonin, dopamine, and norepinephrine. Two large-scale randomized, double-blind, placebo-controlled trials have demonstrated that adjunctive L-methylfolate at 15 mg/day significantly improves treatment outcomes in patients with SSRI-resistant major depressive disorder. |
Critical for Pregnancy & Fetal DevelopmentAdequate folate status during the periconceptional period is essential for preventing neural tube defects (NTDs). L-5-MTHF-Ca provides an immediate, bioavailable folate source that does not accumulate as unmetabolized folic acid (UMFA) in circulation-a concern associated with high-dose folic acid supplementation. |
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What is Calcium L-5-Methyltetrahydrofolate Used For?
- Dietary Supplements - The primary application of L-5-MTHF-Ca is as the active folate ingredient in single-ingredient or multivitamin formulations in capsule, tablet, softgel, and gummy formats targeting general wellness, cardiovascular health, and prenatal nutrition.
- Infant Formula & Follow-on Formula - Approved by EFSA as a folate source for infant and follow-on formulas, L-5-MTHF-Ca provides newborns and infants with the biologically active folate form that they are developmentally capable of utilizing.
- Prenatal Vitamins - L-5-MTHF-Ca is increasingly preferred over folic acid in premium prenatal supplement formulations, ensuring immediate folate availability during the critical first weeks of pregnancy when neural tube closure occurs.
- Functional Foods & Beverages - The stabilized calcium salt form is incorporated into fortified foods, nutrition bars, meal replacements, and functional beverages aimed at supporting energy metabolism and cognitive performance.
- Medical Foods & Clinical Nutrition - Used in prescription medical foods for the dietary management of folate-responsive conditions, including hyperhomocysteinemia and depression associated with folate deficiency.
- Sports Nutrition - Emerging applications in sports nutrition leverage the role of L-5-MTHF in red blood cell production, oxygen transport, and methyl group donation for creatine synthesis.
Frequently Asked Questions (FAQ)
Q: What is the difference between Calcium L-5-MTHF and standard folic acid?
Folic acid is a synthetic, oxidized form of folate that must be reduced twice by DHFR and then methylated by MTHFR before becoming active. Calcium L-5-MTHF is already the reduced, methylated, biologically active form-it bypasses all enzymatic conversion steps and is immediately available for cellular use.
Q: Who should use L-5-MTHF instead of folic acid?
L-5-MTHF-Ca is particularly beneficial for: (1) individuals with known MTHFR gene polymorphisms; (2) women planning pregnancy or currently pregnant; (3) individuals taking medications that interfere with folate metabolism; (4) those with elevated homocysteine levels; (5) individuals with depression who are partial or non-responders to antidepressant therapy; and (6) formulators seeking to offer premium, bioactive folate products.
Q: What is the recommended dosage?
Typical supplemental dosages range from 400 μg to 1,000 μg (1 mg) daily for general health and prenatal support, while therapeutic dosages of 7.5 mg to 15 mg daily have been studied in clinical settings for depression adjunctive therapy.
Q: Is Calcium L-5-Methyltetrahydrofolate safe?
Yes. A comprehensive safety evaluation of calcium L-methylfolate has been conducted, including genotoxicity assays, subchronic toxicity studies, and prenatal developmental toxicity assessments. L-5-MTHF-Ca has GRAS status, is approved by EFSA for infant formula, and meets JECFA/FAO food additive specifications.
Q: How should Calcium L-5-MTHF be stored?
L-5-MTHF-Ca is sensitive to heat, light, moisture, and oxidation. Store in a tightly sealed container at 2–8°C, protected from light and moisture. Under recommended storage conditions, the product has a shelf life of 24 months.
Why Choose Huilin Bio-Tech?
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For inquiries, quotations, or sample requests, please contact: sales@huilinbio-tech.com
References
- Pietrzik K, Bailey L, Shane B. Folic acid and L-5-methyltetrahydrofolate: comparison of clinical pharmacokinetics and pharmacodynamics. Clin Pharmacokinet. 2010;49(8):535–548. PMID: 20608755
- Papakostas GI, et al. L-methylfolate as adjunctive therapy for SSRI-resistant major depression. Am J Psychiatry. 2012;169(12):1267–1274. PMID: 23212058
- Lamers Y, et al. Supplementation with [6S]-5-methyltetrahydrofolate or folic acid equally reduces plasma total homocysteine concentrations in healthy women. Am J Clin Nutr 2004;79(3):473-478. PMID:14985224
- Niederberger KE, et al. Safety evaluation of calcium L-methylfolate. Toxicol Rep. 2019;6:1018–1028. PMID: 31673504
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