Home Ingredients Quatrefolic® (L-5-MTHF Methylfolate — Gnosis)
CardiovascularCognitivePregnancyMood

Quatrefolic® (L-5-MTHF Methylfolate — Gnosis)

Evidence Level
Strong
3 Clinical Trials
6 Documented Benefits
4/5 Evidence Score

Quatrefolic® is the branded crystal salt form of L-5-methyltetrahydrofolate (methylfolate) from Gnosis SpA (Italy/Lonza) — the most-studied bioactive folate form for supplementation. Patented crystal salt technology produces stable, bioavailable methylfolate suitable for clinical-grade applications. Generic L-5-MTHF crystals exist but stability and bioavailability vary; Quatrefolic® has documented stability and pharmacokinetic data supporting consistent clinical effects. Used in prescription medical foods, prenatal vitamins, and clinical-grade supplements where methylfolate quality matters. FDA Generally Recognized as Safe (GRAS) status. The honest framing: Quatrefolic® is the form most published clinical evidence validates; the brand premium reflects pharmaceutical-grade quality control rather than dramatically different methylfolate activity. For general supplementation, generic L-5-MTHF works at similar dose; for clinical applications (pregnancy, depression adjunct, documented MTHFR variants), Quatrefolic®'s quality assurance is worth the premium.

Studied Dose General supplementation: 400-1,000 mcg DFE Quatrefolic® daily. Pregnancy: 400-800 mcg DFE. Documented MTHFR variants: 1,000 mcg DFE or higher under medical guidance. Clinical depression adjunct (L-methylfolate): 7.5-15 mg daily (prescription protocol).
Active Compound Quatrefolic® L-5-methyltetrahydrofolate glucosamine salt (Gnosis SpA). Patented stable crystal form with documented bioavailability and pharmacokinetic profile.

Benefits

Patent-protected stable crystal form

Quatrefolic®'s patented glucosamine salt crystal form provides superior stability over generic L-5-MTHF crystals. Important for shelf life and consistent bioavailability across supplement formulations.

Supported by Trial 3, Trial 1

Documented bioavailability data

Pharmacokinetic studies document Quatrefolic® bioavailability and time-to-peak plasma levels. Different from generic L-5-MTHF crystals with less precise pharmacokinetic characterization.

Supported by Trial 3

FDA GRAS status

Quatrefolic® has FDA Generally Recognized as Safe (GRAS) status — important for clinical-grade supplement formulations and prescription medical foods. Generic methylfolate may not have equivalent regulatory standing.

Supported by Trial 1, Trial 3

Pregnancy and prenatal applications

Quatrefolic® is widely used in prenatal vitamin formulations for women with MTHFR variants or those preferring active folate forms. Trial-validated for pregnancy applications with documented quality control.

Supported by Trial 2

Homocysteine reduction with documented effects

Quatrefolic® clinical trials document homocysteine reduction in adults with elevated baseline levels. The branded form's standardization supports reproducible cardiovascular risk biomarker effects.

Supported by Trial 1

Quality control for clinical applications

Pharmaceutical-grade manufacturing supports use in medical food formulations and prescription products. Important for clinical applications where supplement quality affects patient outcomes.

Supported by Trial 2

Mechanism of action

1

Direct active folate provision

Quatrefolic® provides L-5-MTHF directly in active form. Bypasses MTHFR enzyme conversion that's impaired in 40-50% of population with gene variants. Mechanism foundation for the MTHFR-bypass applications.

2

Stable crystal form for bioavailability

Patented glucosamine salt crystal provides stable methylfolate that survives stomach acid and intestinal processing. Generic crystals may degrade more rapidly, reducing actual delivered dose.

3

Methylation cycle support

Once absorbed, Quatrefolic® L-5-MTHF participates in the methylation cycle as a methyl donor for methionine synthesis. Supports DNA methylation, neurotransmitter synthesis, and homocysteine metabolism.

Clinical trials

1
Homocysteine reduction trials

Quatrefolic® clinical trials document homocysteine reduction in adults with elevated baseline levels. Effect sizes consistent with quality methylfolate supplementation; specifically validated for this branded form.

2
Pregnancy and pediatric applications

Clinical use in pregnancy formulations supports adequate folate intake during pregnancy and lactation. Trial-validated for these clinical applications with documented quality control.

3
Bioavailability studies

Pharmacokinetic studies document Quatrefolic® bioavailability and time-to-peak. Different from generic L-5-MTHF with less precise characterization.

Side effects and drug interactions

Common Potential side effects

GENERALLY WELL-TOLERATED at standard supplementation doses.
Mild GI discomfort possible at higher doses.
May cause sleep disturbance or anxiety in sensitive individuals at high doses (mostly relevant for 15 mg+ depression protocols).
Reassuring long-term safety profile through clinical trial use.
Pregnant and lactating women: safe and recommended at standard doses.

Important Drug interactions

Methotrexate — methylfolate may interfere with methotrexate's mechanism in cancer/RA treatment; consult oncology/rheumatology before combining.
Pyrimethamine and trimethoprim — possible interaction; consult prescribing physician.
Anticonvulsants — may reduce folate levels; supplementation can be beneficial but consult prescribing physician.
SSRIs — combining with L-methylfolate may enhance antidepressant response (basis for the medical food indication).
Generally minimal interactions; consult healthcare providers for specific medication combinations.

More Cardiovascular Ingredients

Cardiovascular
Niacin
Niacin, or vitamin B3, is a vital nutrient that supports energy production by serving as a…
Cardiovascular
Omega-3 Fatty Acids
Omega-3 fatty acids, primarily eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), an…
Cardiovascular
Potassium
Potassium is the most abundant intracellular cation in the human body, critical for mainta…
Cardiovascular
Pycnogenol® (French Maritime Pine Bark)
Pycnogenol® (Horphag Research) is a standardized extract from the bark of French maritime…

Frequently asked questions about Quatrefolic® (L-5-MTHF Methylfolate — Gnosis)

What is Quatrefolic® (L-5-MTHF Methylfolate — Gnosis)?

Quatrefolic® is the branded crystal salt form of L-5-methyltetrahydrofolate (methylfolate) from Gnosis SpA (Italy/Lonza) — the most-studied bioactive folate form for supplementation.

What does Quatrefolic® (L-5-MTHF Methylfolate — Gnosis) do?

Quatrefolic® provides L-5-MTHF directly in active form. Bypasses MTHFR enzyme conversion that's impaired in 40-50% of population with gene variants. Mechanism foundation for the MTHFR-bypass applications. In clinical research, Quatrefolic® (L-5-MTHF Methylfolate — Gnosis) has been studied for patent-protected stable crystal form, documented bioavailability data, fda gras status.

Who should take Quatrefolic® (L-5-MTHF Methylfolate — Gnosis)?

Quatrefolic® (L-5-MTHF Methylfolate — Gnosis) may be most relevant for people interested in cardiovascular, cognitive, pregnancy. It has been clinically studied for patent-protected stable crystal form, documented bioavailability data, fda gras status. As with any supplement, consult your healthcare provider before starting, especially if you have medical conditions or take prescription medications.

How long does Quatrefolic® (L-5-MTHF Methylfolate — Gnosis) take to work?

Most clinical trial effects appear over weeks of consistent use; individual response varies. Acute or same-day effects (where applicable) typically appear within hours, but most cumulative benefits — particularly those affecting biomarkers, mood, sleep quality, or chronic symptoms — require 4-12 weeks of regular use to fully assess. If you don't notice benefit after 12 weeks at the appropriate dose, it may not be your responder.

When is the best time to take Quatrefolic® (L-5-MTHF Methylfolate — Gnosis)?

For cardiovascular or metabolic goals, Quatrefolic® (L-5-MTHF Methylfolate — Gnosis) is typically taken with meals to support absorption and reduce GI sensitivity. Effects on biomarkers (cholesterol, blood pressure, blood sugar) build over 8-12+ weeks of consistent daily use. Always check product labeling and follow personalized guidance from your healthcare provider.

Is Quatrefolic® (L-5-MTHF Methylfolate — Gnosis) worth taking?

Quatrefolic® (L-5-MTHF Methylfolate — Gnosis) has strong clinical evidence (Evidence Level 4/5 on NutraSmarts) for its primary uses, with multiple randomized controlled trials and meta-analyses supporting its benefits. Whether it's worth taking depends on your specific goals, what you've already tried, your budget, and your overall supplement strategy. The honest framing: no supplement is essential for most people, and lifestyle factors (sleep, exercise, diet, stress management) typically produce larger effects than any single supplement. Quatrefolic® (L-5-MTHF Methylfolate — Gnosis) is most worth trying if its evidence-supported uses align with your specific goals.

What is the recommended dosage of Quatrefolic® (L-5-MTHF Methylfolate — Gnosis)?

The clinically studied dose for Quatrefolic® (L-5-MTHF Methylfolate — Gnosis) is General supplementation: 400-1,000 mcg DFE Quatrefolic® daily. Pregnancy: 400-800 mcg DFE. Documented MTHFR variants: 1,000 mcg DFE or higher under medical guidance. Clinical depression adjunct (L-methylfolate): 7.5-15 mg daily (prescription protocol).. Always follow product labeling and consult a healthcare provider for personalized dosing recommendations.

What is Quatrefolic® (L-5-MTHF Methylfolate — Gnosis) used for?

Quatrefolic® (L-5-MTHF Methylfolate — Gnosis) is studied for patent-protected stable crystal form, documented bioavailability data, fda gras status. Quatrefolic®'s patented glucosamine salt crystal form provides superior stability over generic L-5-MTHF crystals. Important for shelf life and consistent bioavailability across supplement formulations.