Methylfolate (L-5-MTHF, Active Vitamin B9)
Methylfolate (L-5-MTHF) is the biologically active form of folate (vitamin B9) that bypasses the need for genetic conversion, making it more readily available for cellular functions including DNA synthesis, neurotransmitter production, and homocysteine metabolism. Unlike synthetic folic acid, methylfolate can be utilized even by individuals with MTHFR genetic variants that impair folate metabolism. Dietary supplements are not FDA-approved to diagnose, treat, cure, or prevent any disease. Consult your doctor before starting any supplement.
Key Takeaways
- Methylfolate (L-5-MTHF) is the active form of vitamin B9 that bypasses genetic conversion issues, making it superior to synthetic folic acid for those with MTHFR gene variants (affecting ~40% of Americans)
- Supports cardiovascular health by reducing homocysteine levels and may reduce stroke risk by 15% according to meta-analysis of nearly 97,000 participants
- May enhance mood and cognitive function by supporting neurotransmitter production (serotonin, dopamine), particularly beneficial for treatment-resistant depression
- Typical dosages range from 400-800 mcg daily, with peak blood levels reached within 1-3 hours and significantly higher bioavailability than folic acid
- Water-soluble vitamin with relatively few side effects, but requires caution in those with B12 deficiency as it can mask symptoms
How to Take
Typical Dosage
400-1000 mcg daily based on clinical research. Medical supervision may use higher doses up to 15mg for specific conditions like treatment-resistant depression. Start with lower doses as methylfolate can cause overstimulation in sensitive individuals.
When to Take
With or without food, preferably in the morning as it may be energizing. Can be taken with other B-vitamins for synergistic effects.
Why It Matters for Ages 50+
Adults over 50 have decreased absorption of folate from food due to reduced stomach acid production and age-related digestive changes. Methylfolate becomes particularly important as genetic variations in folate metabolism (MTHFR) become more clinically significant with age, affecting homocysteine levels and cardiovascular health. The active form bypasses age-related metabolic inefficiencies.
What to Look For
- Look for '6(S)-5-MTHF' or 'L-5-MTHF' forms specifically, which show superior absorption and bioavailability compared to other folate forms
- Choose third-party tested products with USP or NSF certification to ensure purity and potency verification
- Verify the supplement is free from synthetic folic acid, which can interfere with methylfolate metabolism
- Select products stored in light-resistant containers as folate compounds can degrade when exposed to light and heat
- Consider starting with lower doses (400 mcg) to assess tolerance before increasing to therapeutic levels
Potential Interactions
Be aware of these potential interactions:
- Anticonvulsants (phenytoin, carbamazepine): Methylfolate may reduce effectiveness of seizure medications
- Methotrexate: High-dose folate may interfere with this medication's therapeutic effects
- Antidepressants (SSRIs, SNRIs): May enhance effects or cause agitation - monitor mood changes closely
- Proton pump inhibitors: Long-term PPI use reduces folate absorption, increasing need for supplementation
- Metformin: Long-term use may reduce B-vitamin absorption including folate
- Sulfasalazine: May reduce folate absorption and increase supplementation needs
Who Should Avoid This Supplement
- Individuals with untreated or undiagnosed B12 deficiency, as methylfolate can mask B12 deficiency symptoms while allowing neurological damage to progress
- People with active cancer receiving methotrexate or other folate-antagonist chemotherapy treatments
- Those with bipolar disorder or history of mania, as methylfolate may trigger manic episodes in susceptible individuals
- Individuals with seizure disorders taking anticonvulsant medications without medical supervision
Recommended by Experts
“Essential for DNA repair, cardiovascular health, and cognitive function”
Frequently Asked Questions
Methylfolate is the bioactive form your body can use immediately, while folic acid is synthetic and requires conversion through enzymes that don't work properly in 40% of people with MTHFR gene variants. Methylfolate achieves 7 times higher blood levels than folic acid.
Most research supports 400-800 mcg daily for cardiovascular and cognitive benefits. Start with 400 mcg and increase gradually if needed, as some people experience overstimulation with higher initial doses.
Methylfolate can be taken with or without food, but taking it with meals may reduce potential stomach upset. Peak absorption occurs within 1-3 hours regardless of food intake.
Most people tolerate methylfolate well, but some may experience irritability, sleep disturbances, or mood changes, especially at higher doses. These effects are usually dose-dependent and reversible.
Consider methylfolate if you have MTHFR gene variants, don't respond well to folic acid supplements, have elevated homocysteine levels, or experience treatment-resistant depression. Genetic testing can confirm MTHFR status.
While leafy greens and legumes contain natural folates, the amounts and bioavailability are often insufficient for therapeutic benefits, especially for those with genetic variants affecting folate metabolism. Supplementation is typically necessary for optimal levels.