What Is Quatrefolic®? Benefits, Dosing, and What to Look For
February 07, 20263 min read
Quatrefolic® is a patented, fourth-generation folate ingredient that delivers 5-methyltetrahydrofolate (5-MTHF)—the biologically active form of vitamin B9—as a glucosamine salt for superior stability and bioavailability. Unlike synthetic folic acid, Quatrefolic® requires no enzymatic conversion and is immediately usable, making it critical for individuals with MTHFR gene variants.
What Is Quatrefolic®?
Quatrefolic® is a branded form of (6S)-5-methyltetrahydrofolate glucosamine salt, manufactured by Gnosis by Lesaffre. It delivers folate in the same molecular form that circulates in human blood and enters cells for use in methylation reactions, DNA synthesis, and neurotransmitter production.
Folate (vitamin B9) is essential for health, but the term “folate” encompasses many forms. Food folate, synthetic folic acid, and various supplemental 5-MTHF forms all have different absorption profiles and conversion requirements. Quatrefolic® represents the most advanced supplemental folate available, engineered for stability and direct bioactivity.
How Does Quatrefolic® Work?
Synthetic folic acid—the form found in fortified foods and many supplements—must undergo multiple enzymatic conversions before it becomes the active 5-MTHF. The final step is catalyzed by the enzyme MTHFR (methylenetetrahydrofolate reductase). Genetic variants in the MTHFR gene (particularly C677T and A1298C) are common, affecting an estimated 40–60% of the global population and significantly reducing the efficiency of this conversion.
Quatrefolic® bypasses the MTHFR enzyme entirely because it already delivers folate in its final active form. Once absorbed in the small intestine, 5-MTHF from Quatrefolic® directly enters the folate cycle, donating methyl groups to homocysteine (converting it to methionine) and supporting DNA methylation, neurotransmitter synthesis, and cellular repair.
What Does the Research Show?
A pharmacokinetic study published in the European Journal of Clinical Pharmacology found that 5-MTHF was significantly more bioavailable than folic acid, producing higher plasma folate levels over time—especially in individuals carrying MTHFR variants (PubMed: PMID 14985889). This finding is foundational to the argument for using active folate forms.
Research in the Journal of Nutritional Science has demonstrated that unmetabolized folic acid (UMFA)—which accumulates when synthetic folic acid intake exceeds the body’s conversion capacity—may have unintended biological effects. Using 5-MTHF instead of folic acid avoids UMFA accumulation entirely (PubMed: PMID 29707257).
A clinical trial published in the British Journal of Nutrition confirmed that Quatrefolic® supplementation effectively raised red blood cell folate levels and lowered plasma homocysteine in healthy adults, with results comparable to or better than equimolar doses of folic acid (PubMed: PMID 26169781).
Recommended Dosage and Forms
Standard folate recommendations range from 400–800 mcg DFE (Dietary Folate Equivalents) per day for adults, with higher amounts often used during pregnancy. Quatrefolic® is typically dosed in mcg of 5-MTHF and is found in capsule and tablet formats.
When reading supplement labels, note that Quatrefolic® may be listed as “(6S)-5-methyltetrahydrofolic acid glucosamine salt.” Look for the Quatrefolic® logo or name to confirm the branded ingredient. This matters because not all 5-MTHF ingredients use the same salt form or manufacturing process, and stability varies.
Potential Side Effects and Safety
5-MTHF is the natural form of folate used by the body and has an excellent safety profile. Side effects are rare at recommended doses. Unlike high-dose folic acid, 5-MTHF does not cause accumulation of unmetabolized folic acid in the bloodstream.
Individuals taking methotrexate or anti-seizure medications should consult a healthcare provider before supplementing with any form of folate, as folate can affect the efficacy of these drugs.
Where to Find Quatrefolic®
Utzy Naturals uses Quatrefolic® in Essentially-U, the brand’s comprehensive daily multivitamin. By choosing Quatrefolic® over generic folic acid, Utzy Naturals ensures that the folate in Essentially-U is bioavailable regardless of your MTHFR status—a detail that separates quality formulation from the generic approach.
Quatrefolic® is a specific branded form of methylfolate (5-MTHF) delivered as a glucosamine salt for enhanced stability. While other methylfolate products exist, Quatrefolic® is one of the most well-characterized and widely used in premium supplements.
Why not just take folic acid?
Folic acid requires multiple enzymatic conversions to become active 5-MTHF. People with MTHFR gene variants (40–60% of the population) may convert folic acid inefficiently, potentially leading to unmetabolized folic acid in the bloodstream.
How do I know if I have an MTHFR variant?
A simple genetic test from your healthcare provider or a consumer genomics service can identify common MTHFR variants (C677T and A1298C). However, many practitioners now recommend active folate forms like Quatrefolic® as a universal approach.
Is Quatrefolic® safe during pregnancy?
Active folate is critical during pregnancy for fetal neural tube development. Many prenatal vitamins now include 5-MTHF forms. Consult your healthcare provider for personalized guidance on dosing.
Can Quatrefolic® lower homocysteine?
Yes. By donating a methyl group to convert homocysteine into methionine, 5-MTHF from Quatrefolic® directly supports healthy homocysteine metabolism. Clinical studies confirm its effectiveness for this purpose.
*These statements have not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure, or prevent any disease.
