the stable, bio-identical form of folate that circulates in blood.

 L-5-Methyltetrahydrofolate Calcium (L-5-MTHF-Ca)—the stable, bio-identical form of folate that circulates in blood.

1. Potent homocysteine-lowering & cardiovascular support

• Rapid effect in healthy adults. Eight weeks of 400 µg L-5-MTHF lowered serum total homocysteine (tHcy) by ≈25 % and out-performed an isocaloric folinic-acid arm. pubmed.ncbi.nlm.nih.gov

• Low-dose efficacy confirmed. As little as 113 µg day⁻¹ of L-5-MTHF for 12 weeks reduced plasma tHcy to the same extent as 200 µg folic acid in a placebo-controlled crossover trial. pubmed.ncbi.nlm.nih.gov

• Endothelial function. An acute intra-arterial dose (50 nmol min⁻¹) of L-5-MTHF restored flow-mediated dilation and decreased vascular superoxide in human radial arteries, implying improved eNOS coupling—an effect not seen with equimolar folic acid. pubmed.ncbi.nlm.nih.gov

Why it matters: Lowering tHcy and improving NO bioavailability translate into better vascular tone and may reduce long-term cardiovascular risk.

2. Bypassing MTHFR polymorphisms & improving folate status

Up to 40 % of the global population carries the C677T or A1298C MTHFR variants that slow the conversion of folic acid to 5-MTHF. Supplementation with the ready-made form (Quatrefolic® or calcium salt) circumvents this “bottleneck,” producing higher red-cell folate and lower tHcy than folic-acid at equal doses. pmc.ncbi.nlm.nih.gov

3. Reproductive health & pregnancy outcomes

• Assisted reproductive technology (ART). In a 269-patient retrospective study, women given 400 µg day⁻¹ L-5-MTHF + B12 achieved higher clinical-pregnancy (52 % vs 34 %) and live-birth rates (45 % vs 30 %) than those on 400 µg folic acid alone. pubmed.ncbi.nlm.nih.gov

• Neural-tube-defect (NTD) prevention & perinatal folate levels. Prospective data show L-5-MTHF raises maternal plasma folate more efficiently than folic acid and is considered particularly useful for women with MTHFR variants or impaired folate metabolism. pmc.ncbi.nlm.nih.gov

4. Adjunctive therapy for major depressive disorder (MDD)

• Treatment-resistant depression. Two sequential double-blind RCTs demonstrated that 15 mg day⁻¹ L-methylfolate added to SSRIs nearly doubled response rates compared with placebo augmentation (32 % vs 15 %). Meta-analytic reviews now list 15 mg L-MTHF as a provisionally recommended nutraceutical in MDD guidelines. pmc.ncbi.nlm.nih.gov

• Monotherapy pilot. A classic 6-week head-to-head trial found 25 mg L-MTHF produced similar remission rates to 150 mg amitriptyline, with fewer adverse effects. pmc.ncbi.nlm.nih.gov

Mechanistic angle: L-MTHF crosses the blood-brain barrier, donates one-carbon units for monoamine synthesis, and may dampen neuro-inflammation and NMDA-driven excitotoxicity.

5. Emerging benefits & specialty settings

*⬤⬤⬤⬤ = robust RCT/meta-analysis; ⬤⬤⬤◯ = ≥2 RCTs; ⬤⬤◯◯ = single RCT or good observational; ⬤◯◯◯ = pre-clinical or pilot.

Typical supplemental ranges & safety

L-5-MTHF is well-tolerated; unlike high-dose folic acid it does not mask B-12 deficiency or accumulate as unmetabolized folic acid. Mild GI discomfort and insomnia are uncommon (<2 %). Always pair with adequate B-12 (methyl- or hydroxo-cobalamin) to maintain one-carbon balance.