10 Best Methylfolate Supplements (2026) Reviewed
Methylfolate has become one of the most talked-about supplements in the health and wellness community, and for good reason. Unlike synthetic folic acid, L-methylfolate (also known as 5-MTHF) is the biologically active form of folate that your body can use immediately—no conversion required. This is particularly important for the estimated 40-60% of the population with MTHFR gene variations that may limit their ability to convert folic acid into its usable form.
Finding the right methylfolate supplement, however, can be overwhelming. With various forms (Quatrefolic, Metafolin, calcium salt, glucosamine salt), dosages ranging from 400 mcg to 15 mg, and quality varying significantly between brands, choosing the wrong product means potentially wasting money on an ineffective supplement. We spent weeks researching methylfolate formulations, analyzing patented ingredient forms, and evaluating third-party testing protocols to identify the supplements that truly deliver on their promises.
Whether you’re looking for methylation support, cardiovascular health, mood balance, or prenatal nutrition, this guide covers the best methylfolate supplements available in 2026 across every price point and use case.
Table of Contents
- Quick Comparison Table
- Types of Methylfolate: Which Form is Best?
- Detailed Product Reviews
- Buying Guide: What to Look For
- How to Take Methylfolate
- Potential Benefits of Methylfolate
- Safety Considerations
- Frequently Asked Questions
- The Bottom Line
Quick Comparison Table
| Product | Form | Serving Size | Key Differentiator | Best For | Winner |
|---|---|---|---|---|---|
| Thorne 5-MTHF 1mg | Capsules | 1 mg (1,700 mcg DFE) | Clinical-grade purity, trusted by pro athletes | Overall quality | 🏆 TOP PICK |
| NOW Foods Methyl Folate 1000 mcg | Tablets | 1,000 mcg (1,667 mcg DFE) | Quatrefolic form, excellent value | Budget-conscious buyers | 🥇 Best Budget |
| Jarrow Formulas Methyl Folate 1000 mcg | Capsules | 1,000 mcg (1,667 mcg DFE) | Quatrefolic, 100-day supply | Value seekers | 🥇 Best Value |
| Pure Encapsulations Folate 1000 | Capsules | 1,000 mcg (1,667 mcg DFE) | Metafolin, hypoallergenic formula | Sensitive individuals | 🥇 Best Hypoallergenic |
| Seeking Health L-5-MTHF 1mg | Capsules | 1 mg (1,700 mcg DFE) | Dr. Ben Lynch formulated, MTHFR-focused | MTHFR support | 🥇 Best for MTHFR |
| Life Extension Optimized Folate | Tablets | 1,700 mcg DFE | Research-backed, cardiovascular focus | Heart & brain health | 🥇 Best for Cardiovascular |
| Doctor’s Best Fully Active Folate 400 mcg | Capsules | 400 mcg (667 mcg DFE) | Quatrefolic with Vitamin C, gentle dose | Beginners | 🥇 Best Starter Dose |
| Carlyle L-Methylfolate 15mg | Capsules | 15 mg (25,000 mcg DFE) | High potency, value pricing | High-dose needs | 🥇 Best High Potency |
| Designs for Health L-5-MTHF 5mg | Capsules | 5 mg (8,500 mcg DFE) | Practitioner-grade Quatrefolic | Clinical use | 🥇 Best Practitioner Grade |
| Triquetra Health L-Methylfolate 15mg | Capsules | 15 mg + B12 | Includes methylcobalamin B12 cofactor | Complete methylation | 🥇 Best with B12 |
Note: Product details and formulations may change. Always verify current information on Amazon before purchasing.
Types of Methylfolate: Which Form is Best?
Not all methylfolate supplements are created equal. The form of methylfolate used in a supplement can significantly impact its stability, absorption, and effectiveness. Here’s what you need to know about the main forms:
Quatrefolic (Glucosamine Salt)
Quatrefolic is a fourth-generation folate that binds L-5-MTHF to glucosamine (non-shellfish derived). Research suggests it may have higher initial bioavailability than calcium salt forms, meaning it becomes available in the bloodstream faster. However, some stability studies indicate it may degrade more quickly over time compared to crystalline calcium salt forms. Many popular brands including Jarrow Formulas, NOW Foods, and Seeking Health use Quatrefolic.
Metafolin (Calcium Salt – Type I Crystalline)
Metafolin was the first patented form of L-methylfolate, developed by Merck. It uses a crystalline calcium salt structure that provides excellent long-term stability. Brands like Pure Encapsulations and Solgar typically use Metafolin. The crystalline structure helps maintain potency throughout the product’s shelf life.
Generic L-5-MTHF Calcium Salt
Some supplements use generic calcium salt forms of methylfolate. While these can still be effective, quality and stability may vary more between manufacturers. Look for products that specify they use the (6S) or “L” isomer, which is the biologically active form.
Which Form Should You Choose?
For most people, both Quatrefolic and Metafolin are excellent choices. The differences in bioavailability are relatively minor, and both forms have demonstrated effectiveness in clinical research. More important than the specific patented form is choosing a reputable brand with third-party testing and proper storage practices.
Detailed Product Reviews
Thorne 5-MTHF 1mg — Best Overall
Thorne’s 5-MTHF stands out as our top pick for its exceptional quality standards, clinical-grade formulation, and widespread trust among healthcare practitioners and professional athletes alike.
Thorne has built a reputation as one of the most trusted supplement brands in the industry, partnering with Mayo Clinic on wellness research and serving as the official supplement partner for multiple U.S. Olympic teams. Their 5-MTHF supplement delivers 1 mg (1,700 mcg DFE) of the active, tissue-ready form of folate in a clean, hypoallergenic formula.
What sets Thorne apart is their commitment to purity. Every batch undergoes four rounds of testing, and the company maintains NSF Certified for Sport status—meaning their products are rigorously tested for banned substances. The capsules contain no unnecessary fillers, making them suitable for individuals with sensitivities to common allergens.
The 1 mg dosage is appropriate for most people looking to support healthy methylation, cardiovascular function, and nervous system health. Thorne also offers 5 mg and 15 mg versions for those who need higher doses under healthcare provider guidance.
Key Specifications:
- Form: L-5-Methyltetrahydrofolate
- Dosage: 1 mg (1,700 mcg DFE) per capsule
- Servings: 60 capsules
- Certifications: NSF Certified for Sport, cGMP
- Free from: Gluten, dairy, soy, artificial preservatives
Considerations: Premium pricing may be a barrier for some buyers, though the quality justifies the cost for those who prioritize purity.
Jarrow Formulas Methyl Folate 1000 mcg — Best Value
Jarrow Formulas combines scientific formulation with excellent value, delivering a 100-day supply of Quatrefolic methylfolate in easy-to-take vegetarian capsules.
Jarrow Formulas has earned its reputation through decades of science-based supplement development. Their Methyl Folate capsules feature Quatrefolic—the fourth-generation methylfolate known for its high bioavailability and stability.
The 100-capsule bottle provides exceptional value, and the vegetarian capsules are free from common allergens including wheat, gluten, soybeans, dairy, eggs, fish, shellfish, and tree nuts. This makes it one of the most accessible methylfolate supplements for people with dietary restrictions.
The 1,000 mcg dosage (1,667 mcg DFE) aligns with research-supported levels for general methylation support while remaining well within safe daily intake limits.
Key Specifications:
- Form: Quatrefolic (6S)-5-MTHF glucosamine salt
- Dosage: 1,000 mcg (1,667 mcg DFE) per capsule
- Servings: 100 vegetarian capsules
- Certifications: cGMP, Non-GMO
- Free from: Wheat, gluten, soy, dairy, egg, fish, shellfish, nuts
Considerations: Some users report preferring calcium salt forms for long-term stability; the glucosamine salt form may require attention to proper storage.
Pure Encapsulations Folate 1000 — Best Hypoallergenic
Pure Encapsulations sets the gold standard for hypoallergenic supplements, using Metafolin in a formula specifically designed for individuals with multiple sensitivities.
For individuals with food sensitivities, chemical sensitivities, or autoimmune conditions, finding a truly clean supplement can be challenging. Pure Encapsulations addresses this need with their commitment to eliminating unnecessary additives, coatings, and common allergens from all their products.
Their Folate 1000 uses Metafolin—the naturally occurring, universally metabolized form of folate developed by Merck. The formula contains only hypoallergenic plant fiber (cellulose) and vegetarian capsule shell, with no artificial colors, flavors, or preservatives.
Pure Encapsulations is a preferred brand among integrative and functional medicine practitioners, and their products undergo rigorous third-party testing for both purity and potency.
Key Specifications:
- Form: Metafolin L-5-MTHF calcium salt
- Dosage: 1,000 mcg (1,667 mcg DFE) per capsule
- Servings: 90 vegetarian capsules
- Certifications: Third-party tested, GMO-free
- Free from: Wheat, eggs, tree nuts, peanuts, gluten, artificial colors/flavors/sweeteners, coatings, shellacs
Considerations: Higher price point than some alternatives; the minimal excipient formula may result in slightly less shelf stability than products with stabilizers.
Seeking Health L-5-MTHF 1mg — Best for MTHFR Support
Formulated by Dr. Ben Lynch, a leading expert on MTHFR gene variants, Seeking Health’s L-5-MTHF is specifically designed for individuals who need targeted methylation support.
Seeking Health was founded by Dr. Ben Lynch, author of “Dirty Genes” and one of the world’s foremost authorities on the MTHFR gene mutation and methylation. His personal experience with methylation issues led him to create supplements specifically formulated for people with these concerns.
The L-5-MTHF capsules use Quatrefolic and are formulated without folic acid—important for individuals whose bodies cannot efficiently process synthetic folic acid. The company never uses folic acid in any of their products, making their entire line suitable for those with MTHFR variants.
Each batch is third-party tested, and the capsules are free from common allergens and artificial ingredients. Seeking Health also offers this product in lozenge form for those who prefer sublingual absorption.
Key Specifications:
- Form: Quatrefolic (6S)-5-MTHF glucosamine salt
- Dosage: 1 mg (1,700 mcg DFE) per capsule
- Servings: 60 capsules
- Certifications: Third-party tested, cGMP
- Free from: GMOs, gluten, eggs, fish, shellfish, tree nuts, peanuts, wheat, soy
Considerations: The company recommends not taking within 5 hours of bedtime as it may interfere with sleep in some individuals.
Life Extension Optimized Folate — Best for Cardiovascular Health
Life Extension backs their Optimized Folate with decades of research into cardiovascular and cognitive health, delivering a science-forward formula for health-conscious consumers.
Life Extension has been at the forefront of longevity research since 1980, funding and publishing studies on nutrients that support healthy aging. Their Optimized Folate reflects this research-driven approach, providing the bioactive 5-MTHF form specifically for cardiovascular and cognitive support.
The formula delivers 1,700 mcg DFE per vegetarian tablet—a dosage supported by research showing benefits for maintaining healthy homocysteine levels. Unlike folic acid, the 5-MTHF in this formula can cross the blood-brain barrier, making it particularly relevant for cognitive health applications.
Life Extension provides a Certificate of Analysis for every product, and their manufacturing facilities exceed cGMP standards.
Key Specifications:
- Form: (6S)-5-Methyltetrahydrofolate calcium salt
- Dosage: 1,700 mcg DFE per tablet
- Servings: 100 vegetarian tablets
- Certifications: Certificate of Analysis available, Non-GMO
- Free from: Gluten
Considerations: Tablet form may be harder to split for those wanting to adjust dosage; Life Extension recommends consulting a healthcare provider if at risk of vitamin B12 deficiency.
Doctor’s Best Fully Active Folate 400 mcg — Best Starter Dose
Doctor’s Best provides an ideal entry-level dose of Quatrefolic methylfolate, perfect for those new to supplementation or wanting to start conservatively.
Starting methylfolate supplementation at a lower dose is often recommended, especially for individuals who may be sensitive to methylation support. Doctor’s Best Fully Active Folate provides 400 mcg of Quatrefolic—enough to meet the RDA while allowing users to assess their response before increasing dosage.
A unique feature of this formula is the inclusion of 40 mg of Vitamin C (ascorbic acid), which may help with folate stability and absorption. The vegetarian capsules are suitable for most dietary preferences.
Doctor’s Best has been producing science-based nutritional supplements since 1990, using only well-researched, branded ingredients.
Key Specifications:
- Form: Quatrefolic (6S)-5-MTHF glucosamine salt
- Dosage: 400 mcg (667 mcg DFE) per capsule
- Additional: 40 mg Vitamin C
- Servings: 90 vegetarian capsules
- Certifications: Non-GMO, Vegan
Considerations: The 400 mcg dose may be insufficient for individuals with higher folate needs; those requiring therapeutic doses will need to take multiple capsules or choose a higher-potency product.
Carlyle L-Methylfolate 15mg — Best High Potency
Carlyle delivers maximum-strength methylfolate at an accessible price point, ideal for individuals under healthcare supervision who require high-dose supplementation.
For individuals with significant methylation challenges or those whose healthcare providers have recommended high-dose folate, Carlyle’s 15 mg L-Methylfolate offers a potent solution at exceptional value. The 120-capsule bottle provides a four-month supply of therapeutic-level methylfolate.
Carlyle is a family-owned company with over 40 years of experience in the supplement industry. Their Opti-Folate line uses quick-release capsules designed for rapid absorption, and all products are laboratory tested for quality and purity.
The 15 mg (25,000 mcg DFE) dosage should only be used under healthcare provider guidance, as high-dose methylfolate may not be appropriate for everyone and can cause side effects in some individuals.
Key Specifications:
- Form: L-Methylfolate
- Dosage: 15 mg (25,000 mcg DFE) per capsule
- Servings: 120 quick-release capsules
- Certifications: Laboratory tested, Non-GMO
- Free from: Gluten, wheat, yeast, lactose, soy, artificial flavors, preservatives
Considerations: High-potency formula should only be used under healthcare supervision; may mask vitamin B12 deficiency symptoms; not appropriate for general wellness supplementation.
Designs for Health L-5-MTHF 5mg — Best Practitioner Grade
As the #1 practitioner-recommended supplement brand, Designs for Health delivers clinical-strength Quatrefolic methylfolate trusted by functional medicine professionals.
Designs for Health has earned its reputation as a practitioner-focused brand by maintaining rigorous quality standards and formulating products based on clinical research. Their L-5-MTHF provides 5 mg (8,500 mcg DFE) of patented Quatrefolic—a mid-range therapeutic dose often recommended by integrative medicine practitioners.
A distinctive feature of this formula is the addition of organic spinach powder, which gives the capsules their characteristic green color while providing a whole-food cofactor. The company uses only the highest quality raw materials and conducts extensive testing on every batch.
While Designs for Health products are often dispensed through healthcare practitioners, they are also available directly to consumers who understand the appropriate use of clinical-strength supplements.
Key Specifications:
- Form: Quatrefolic (6S)-5-MTHF glucosamine salt
- Dosage: 5 mg (8,500 mcg DFE) per capsule
- Additional: Organic spinach powder
- Servings: 60 vegetarian capsules
- Certifications: Third-party tested, Non-GMO
- Free from: Gluten
Considerations: Higher price point reflects practitioner-grade quality; 5 mg dose is more than most people need for general wellness and should be used with guidance.
Triquetra Health L-Methylfolate 15mg Plus B12 — Best with B12 Cofactor
Triquetra Health combines high-potency methylfolate with its essential cofactor methylcobalamin B12, addressing the fact that these two nutrients work synergistically in the body’s methylation processes.
Methylfolate and methylcobalamin B12 have a co-dependent relationship in the body—methylfolate cannot complete the methylation cycle and break down homocysteine without adequate B12. Triquetra Health addresses this by combining 15 mg of L-methylfolate with methylcobalamin B12 in a single capsule.
This combination approach is particularly valuable for individuals with both MTHFR variants and absorption issues, as well as those wanting to support comprehensive methylation without taking multiple supplements. The formula uses the 5-MTHF calcium salt form known for stability.
Triquetra Health focuses exclusively on methylation support supplements, bringing specialized expertise to their formulations.
Key Specifications:
- Form: L-5-MTHF calcium salt
- Dosage: 15 mg methylfolate + methylcobalamin B12 per capsule
- Servings: 60 capsules
- Certifications: GMP manufactured
- Free from: Gluten
Considerations: High-potency formula requires healthcare supervision; individuals taking separate B12 supplements should be aware of total B12 intake; some users may find the combination dose inflexible.
Buying Guide: What to Look For in a Methylfolate Supplement
Quality Indicators
Patented Ingredient Forms: Look for supplements using branded methylfolate forms like Quatrefolic, Metafolin, or Magnafolate. These patented ingredients come with quality guarantees and research backing that generic forms may lack.
Third-Party Testing: Reputable brands conduct independent testing for purity, potency, and contaminants. Look for products that display testing certifications or offer Certificates of Analysis.
Correct Isomer: Ensure the label specifies L-methylfolate, (6S)-5-MTHF, or L-5-MTHF. The “L” or “6S” designation indicates the biologically active form. Products listing just “5-MTHF” without clarification may contain inactive forms.
Clean Formulation: Minimal inactive ingredients reduce the risk of reactions and indicate quality manufacturing. Avoid products with artificial colors, unnecessary fillers, or common allergens unless you know you tolerate them.
Certifications That Matter
GMP (Good Manufacturing Practices): Indicates the facility follows FDA-recognized quality standards for supplement manufacturing.
NSF International: Independent testing organization that verifies products contain what they claim and are free from contaminants.
NSF Certified for Sport: Especially important for athletes; confirms products are free from banned substances.
Non-GMO Project Verified: Third-party verification that products are free from genetically modified ingredients.
Red Flags to Avoid
- Products listing only “folate” or “folic acid” without specifying methylfolate
- Unusually low prices that suggest inferior ingredients
- Missing or vague information about ingredient sources
- No third-party testing claims or certifications
- Products containing both folic acid and methylfolate (unnecessary and potentially problematic)
- Outrageous health claims or promises of disease treatment
Dosage Selection Guide
400-800 mcg: General wellness maintenance, prenatal supplementation (with healthcare guidance), those new to methylfolate
1-5 mg: Individuals with confirmed MTHFR variants, those with elevated homocysteine levels, mood support (under healthcare guidance)
5-15 mg: Clinical applications under healthcare provider supervision only; may be recommended for specific therapeutic purposes
How to Take Methylfolate
Recommended Dosage
The Recommended Dietary Allowance (RDA) for folate in adults is 400 mcg DFE daily, increasing to 600 mcg DFE during pregnancy. However, methylfolate supplements often provide higher amounts because they may be used to address specific health concerns beyond basic nutritional needs.
For general supplementation, 400-1,000 mcg of methylfolate daily is typically appropriate. Higher doses (1-15 mg) should only be used under healthcare provider guidance based on individual testing and health needs.
Best Time to Take Methylfolate
Methylfolate can generally be taken at any time of day with or without food. However, some individuals find that taking methylfolate in the morning works best, as it may affect energy levels. Several brands recommend avoiding methylfolate within 5 hours of bedtime, as some people report sleep disturbances when taking it late in the day.
Usage Tips for Different Forms
Capsules and Tablets: Take with a full glass of water. May be taken with food if stomach upset occurs.
Lozenges: Allow to dissolve slowly under the tongue for sublingual absorption. Do not chew or swallow whole.
Liquid Drops: Follow product-specific directions; typically taken directly under the tongue or mixed with a small amount of water.
Duration and Cycling
Methylfolate is generally safe for long-term daily use, as it is the natural form of folate used by the body. Unlike some supplements, there is typically no need to cycle methylfolate. However, if you experience side effects, your healthcare provider may recommend adjusting the dose or taking breaks.
It may take several weeks to notice the effects of methylfolate supplementation, particularly for mood-related benefits. Consistent daily use is more important than specific timing.
Potential Benefits of Methylfolate
Research suggests methylfolate may support several aspects of health. Here’s what the science indicates:
Methylation Support
Methylfolate is essential for the methylation cycle—a biochemical process that occurs in every cell of the body. Proper methylation is involved in DNA synthesis and repair, neurotransmitter production, detoxification processes, and gene expression regulation. Individuals with MTHFR gene variants may have reduced ability to convert folic acid to methylfolate, making direct supplementation potentially beneficial.
Cardiovascular Health
Folate helps metabolize homocysteine, an amino acid that, when elevated, has been associated with cardiovascular concerns. Studies have shown that methylfolate supplementation may help maintain healthy homocysteine levels already within normal range, potentially supporting heart health. A study published in research literature found that 400 mcg of Quatrefolic, combined with vitamins B6 and B12, was more effective at reducing homocysteine than high-dose folic acid alone.
Mood and Cognitive Function
Methylfolate crosses the blood-brain barrier and is involved in the production of neurotransmitters including serotonin, dopamine, and norepinephrine. Some research suggests that methylfolate supplementation may support mood balance, particularly in individuals with certain genetic variations. High-dose methylfolate (7.5-15 mg) has been studied as an adjunct to conventional treatments for mood concerns, though this use should only be pursued under healthcare provider supervision.
Prenatal Health
Adequate folate is critical during pregnancy for proper fetal development, particularly neural tube formation in early pregnancy. While folic acid has been the traditional recommendation, methylfolate may be preferable for women with MTHFR variants or those who want to avoid unconverted folic acid. Pregnant women should consult their healthcare provider before choosing a folate form and dosage.
Safety Considerations
Potential Side Effects
While methylfolate is generally well-tolerated, some individuals may experience side effects, particularly when starting supplementation or taking higher doses:
- Irritability or mood changes
- Headaches
- Difficulty sleeping (insomnia)
- Nausea or digestive discomfort
- Muscle aches or joint pain
- Skin rashes (rare)
- Anxiety or restlessness
These effects often indicate the dose is too high or that methylfolate is being processed too quickly. Reducing the dose or taking methylfolate with other B vitamins (particularly B12, B6, and riboflavin) may help.
Who Should Avoid or Use Caution
Individuals with bipolar disorder: High-dose methylfolate may trigger manic episodes in some individuals; use only under psychiatric supervision.
Those taking anticonvulsants: Methylfolate may interact with certain anti-seizure medications; consult your healthcare provider.
People on methotrexate for cancer: 5-MTHF supplementation is not recommended during methotrexate cancer therapy as it may interfere with treatment effectiveness. (Note: This does not apply to methotrexate used for autoimmune conditions.)
Individuals with vitamin B12 deficiency: High-dose folate may mask symptoms of B12 deficiency, potentially allowing neurological damage to progress undetected. Always ensure adequate B12 status before taking high-dose methylfolate.
Drug Interactions
Methylfolate may interact with several medications including certain anti-seizure drugs (phenobarbital, phenytoin, primidone), methotrexate, and some antibiotics. Always inform your healthcare provider and pharmacist about all supplements you take.
When to Consult a Healthcare Provider
- Before starting methylfolate if you take any prescription medications
- If you’re pregnant, planning pregnancy, or breastfeeding
- If you have a history of mood disorders
- Before using doses above 1 mg daily
- If you experience persistent side effects
- If you want to use methylfolate for a specific health condition
Frequently Asked Questions
What is the difference between folic acid and methylfolate?
Folic acid is the synthetic, oxidized form of folate commonly used in fortified foods and basic supplements. It must be converted through multiple enzymatic steps in the body to become usable methylfolate. L-methylfolate (5-MTHF) is the biologically active form that requires no conversion and can be used immediately by the body. This is particularly important for individuals with MTHFR gene variants who may have reduced ability to convert folic acid.
How do I know if I have an MTHFR mutation?
MTHFR gene variants can be identified through genetic testing, either through healthcare providers or direct-to-consumer testing services. Common variants include C677T and A1298C. However, having an MTHFR variant doesn’t necessarily mean you need supplementation—many people with these variants maintain adequate folate status through diet alone. Testing homocysteine levels can provide functional insight into whether supplementation may be beneficial.
Can I take methylfolate while pregnant?
Methylfolate can be an appropriate choice during pregnancy, and some prenatal vitamins now include it instead of or in addition to folic acid. However, the standard recommendation for pregnancy remains 400-800 mcg of folate daily (from any source). Consult your healthcare provider before choosing between folic acid and methylfolate during pregnancy.
How long does it take to notice benefits from methylfolate?
Some individuals notice effects within days to weeks, particularly in terms of energy levels. However, full benefits for mood support or homocysteine reduction may take 4-12 weeks of consistent supplementation. Patience and consistent dosing are important.
Is it possible to take too much methylfolate?
Yes. While methylfolate doesn’t have an established tolerable upper intake level like folic acid (which is 1,000 mcg daily for adults), high doses can cause side effects in some individuals. More is not always better with methylfolate—starting low and increasing gradually is the safest approach.
Should I take methylfolate with B12?
Methylfolate and B12 work together in the methylation cycle, and many practitioners recommend taking them together. This is particularly important with higher doses of methylfolate, as adequate B12 is needed to complete the metabolic cycle. If you’re taking methylfolate alone, ensure your diet or a separate supplement provides adequate B12.
What’s the difference between Quatrefolic and Metafolin?
Both are patented, high-quality forms of L-methylfolate. Quatrefolic uses a glucosamine salt, while Metafolin uses a calcium salt. Research suggests Quatrefolic may have slightly faster initial absorption, while Metafolin may have better long-term stability. In practical terms, both are effective choices, and the difference is relatively minor for most users.
Can methylfolate help with depression?
Some research suggests methylfolate may support mood, particularly when used as an adjunct to conventional treatments. High-dose methylfolate (7.5-15 mg) has been studied in this context. However, methylfolate supplements are not treatments for depression, and anyone experiencing depression should work with a healthcare provider. Never replace prescribed medications with supplements without medical guidance.
Why does methylfolate give some people anxiety or irritability?
Some individuals experience “overmethylation” symptoms when taking methylfolate, especially at higher doses. This may manifest as anxiety, irritability, or restlessness. This can happen when methylfolate is taken without adequate B12, or when the dose is too high for an individual’s needs. Reducing the dose or adding cofactors like B12 and niacin often helps.
Is methylfolate safe for children?
Methylfolate can be appropriate for children, but dosing should be determined by a pediatric healthcare provider based on the child’s age, weight, and specific needs. Some children’s multivitamins now include small amounts of methylfolate.
The Bottom Line
Choosing the right methylfolate supplement depends on your specific needs, budget, and health goals. Here are our recommendations based on different use cases:
For most people seeking quality methylfolate: Thorne 5-MTHF 1mg offers exceptional purity and quality from a brand trusted by healthcare practitioners and professional athletes. The 1 mg dose is appropriate for general methylation support.
For budget-conscious buyers: NOW Foods Methyl Folate 1000 mcg delivers the same patented Quatrefolic found in premium products at a fraction of the cost. You don’t have to spend more to get quality methylfolate.
For those with sensitivities: Pure Encapsulations Folate 1000 provides the cleanest, most hypoallergenic formula available, using Metafolin in a minimal-ingredient capsule.
For individuals focused on MTHFR support: Seeking Health L-5-MTHF 1mg comes from the company founded by MTHFR expert Dr. Ben Lynch, specifically formulated for methylation support.
For those needing high-potency options under medical supervision: Carlyle L-Methylfolate 15mg offers therapeutic-level dosing at accessible pricing.
Remember that supplements work best as part of an overall healthy lifestyle. Before starting any new supplement regimen, particularly at higher doses, consult with a healthcare provider who can help determine the appropriate form and dose for your individual needs.
