What Does Methylfolate Do in the Body?

What Does Methylfolate Do in the Body?

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Katie Stone - Naturopath

Written By:

Katie Stone - Naturopath
Kari Asadorian - BSN, RN

Medical Reviewer:

Kari Asadorian - BSN, RN
Jamie Hope - Methyl-Life® Founder

Edited By:

Jamie Hope - Methyl-Life® Founder
Last updated:
How Much Methylfolate Do You Need? Benefits & Dosage Guide for MTHFR & Methylation Source: YouTube.com

What is methylfolate?

Methylfolate is the active form of folate - the form the body can use directly. Other forms of folate - whether from food or supplements - must be converted into methylfolate before they can be used by the body.Methylfolate is the main form of folate in the blood and is vital for many processes that sustain life.1

What does methylfolate do in the body?

Methylfolate is one of the most important nutrients for human health. It plays central roles in metabolic, cardiovascular, neurological and developmental health.

One-carbon metabolism

One-carbon metabolism is a network of biochemical reactions that transfers single-carbon units (tiny chemical groups with one carbon atom) between molecules.2 

These reactions are essential for dozens of bodily processes: providing the building blocks for DNA and RNA, recycling amino acids, recycling homocysteine, regenerating methionine and producing compounds such as S-adenosyl-L-methionine (SAMe) that are required for neurotransmitter production and many other gene-related systems.

Insufficient levels of methylfolate, vitamin B12 or vitamin B6 can result in impaired one-carbon metabolism. This can disrupt growth and development, raise homocysteine and affect cognitive and cardiovascular health.3

Neurotransmitter synthesis

Methylfolate is the only form of folate that can cross the blood-brain-barrier, where it is required as a cofactor in the production of serotonin, dopamine and norepinephrine. These neurotransmitters are required for healthy mood and many other cognitive functions.4

Homocysteine regulation

Methylfolate is required for converting homocysteine into methionine, which is then used to produce neurotransmitters and SAMe. This not only supports brain chemistry but also prevents homocysteine buildup, which has been linked to inflammation, cardiovascular disease, stroke and dementia.5

Fetal development

Methylfolate is essential for healthy development of the fetus. Although folic acid is commonly prescribed during pregnancy, some research suggests methylfolate may be better tolerated and avoids certain negative effects like unmetabolized folic acid (UMFA) build up linked to folic acid.6

Brain health

Folate deficiency can negatively impact DNA repair in neurons, increasing vulnerability to oxidative stress and beta-amyloid toxicity, which can then lead to increased inflammation and higher risk of neurodegenerative diseases such as Alzheimer’s.7

Clinical trials on older adults have shown that supplementation with methylfolate led to improvements in cognitive functions, including mental health and the ability to perform daily activities. These improvements were even greater when methylfolate was combined with vitamins B12 and B6.8

L‐methylfolate, choline and betaine have been shown to mitigate the accumulation of phosphorylated tau (a hallmark of dementia) as well as major cognitive and motor deficits.9

Insomnia relief

Methylfolate plays a critical role in the production of neurotransmitters involved in healthy sleep patterns, particularly dopamine, serotonin and norepinephrine. A 2024 study found that people with MTHFR who took 5 mg L-methylfolate daily showed significant improvement in sleep disturbances and sleep quality.10

Detoxification

Glutathione is the body’s master antioxidant and detoxifier. It neutralizes reactive oxygen species (ROS) and assists in the elimination of toxins via the liver.11

Methylfolate is required for the conversion of homocysteine to methionine, the precursor for cysteine, a critical component in the synthesis of glutathione.12

DNA/RNA synthesis

Methylfolate provides single‑carbon units required for synthesizing purines and thymidylate, the building blocks of DNA and RNA. Without sufficient methylfolate, these one‑carbon transfers are impaired, which slows the production of nucleotides and subsequently affects DNA replication, repair and RNA transcription.13

How does methylfolate work?

Methylfolate’s key role is donating methyl groups - small chemical ‘tags’ that control and activate various biological reactions.

For example, it passes a methyl group to vitamin B12, which then converts homocysteine into methionine. Methionine is then converted into SAMe, the body’s universal methyl donor, which is required for hundreds of reactions that regulate DNA, neurotransmitters, detoxification and cellular repair.

Without methylfolate, none of these downstream processes can happen efficiently. Methylfolate directly influences how genes are switched on or off, how brain chemicals such as serotonin and dopamine are balanced, and the normal function and repair of cells.

Because methylfolate drives one-carbon metabolism, it indirectly supports DNA synthesis, energy production, immune defense, cardiovascular health, mood balance and the control of inflammation.14

Maintaining healthy methylfolate levels can contribute to overall wellbeing and may reduce the risk of many age-related diseases.

What happens if you take too much methylfolate?

There is no established upper limit for methylfolate intake. Clinical use of doses up to 15 mg daily has been shown to be well tolerated. Unlike folic acid, methylfolate does not mask vitamin B12 deficiency. However, it is still best to follow the dosage instructions on the supplement label or from your health practitioner. 

As with any supplement, it’s important not to take more than the required dose.

How long does it take for L-methylfolate to work?

Everyone is different, so the timeframe for methylfolate to work varies from person to person. This can depend on your baseline folate levels, your metabolism, the dosage and the quality of your supplement. Many people report noticeable effects within a few days to weeks.

What does methylfolate do in the body?

Key takeaways

  • Icon Methylfolate is the active form of folate that the body requires for numerous biological processes, including homocysteine metabolism and neurotransmitter production
  • Icon Methylfolate is the only form of folate that can cross the blood-brainbarrier to perform its functions
  • Icon Everyone needs methylfolate at every stage in life

Product Recommendations

5 Methylfolate: 5-mthf L-Methylfolate 5 mg

5 Methylfolate: 5-mthf L-Methylfolate 5 mg

$44.00

  • Bioactive 5 Methylfolate That Crosses Blood-Brain Barrier 3
  • Supports Cardiovascular Function 5 & Brain Health 4
  • 3rd-Party Tested for Purity, Potency & Safety
  • 90 Vegan, Non-GMO, Chewable Mint Tablets

Frequently Asked Questions about methylfolate

What is methylfolate?

L-methylfolate is the active bioidentical form of folate that the body requires for numerous biological processes, including recycling homocysteine and creating neurotransmitters.

Is methylfolate good for you?

Yes, methylfolate is good for you. It is an essential nutrient involved in gene regulation, neurotransmitter production, homocysteine conversion, cognitive function and many other processes that support the body and mind.

References

  1. Lorena Carboni; "Active Folate Versus Folic Acid: The Role of 5-MTHF (Methylfolate) in Human Health"; Integrative medicine; 2022 Jul

    https://pmc.ncbi.nlm.nih.gov/articles/PMC9380836/

  2. Krista S Crider, Thomas P Yang, Robert J Berry, Lynn B Bailey; "Folate and DNA Methylation: A Review of Molecular Mechanisms and the Evidence for Folate's Role"; Advances in nutrition; 2012 Jan

    https://pmc.ncbi.nlm.nih.gov/articles/PMC3262611/

  3. Gregory S Ducker, Joshua D Rabinowitz; "One-Carbon Metabolism in Health and Disease"; Cell metabolism; 2018 Jan

    http://pmc.ncbi.nlm.nih.gov/articles/PMC5353360/

  4. Lorena Carboni; "Active Folate Versus Folic Acid: The Role of 5-MTHF (Methylfolate) in Human Health"; Integrative medicine; 2022 Jul

    https://pmc.ncbi.nlm.nih.gov/articles/PMC9380836/

  5. Phillip Son, Lindsay Lewis; "Hyperhomocysteinemia"; StatPearls [Internet].; 2022 May

    https://www.ncbi.nlm.nih.gov/books/NBK554408/

  6. Enrico Ferrazzi, Giulia Tiso, Daniela Di Martino; "Folic acid versus 5- methyl tetrahydrofolate supplementation in pregnancy"; European journal of obstetrics, gynecology, and reproductive biology; 2020 Oct

    https://pubmed.ncbi.nlm.nih.gov/32868164/

  7. Frank L Heppner, Richard M Ransohoff, Burkhard Becher; "Immune attack: the role of inflammation in Alzheimer disease"; Nature reviews. Neuroscience.; 2015 Jun

    https://pubmed.ncbi.nlm.nih.gov/25991443/

  8. Celeste A de Jager, Abderrahim Oulhaj, Robin Jacoby, Helga Refsum, A David Smith; "Cognitive and clinical outcomes of homocysteine-lowering B-vitamin treatment in mild cognitive impairment: a randomized controlled trial"; International journal of geriatric psychiatry; 2012 Jun

    https://pubmed.ncbi.nlm.nih.gov/21780182/

  9. Annika van Hummel, Goce Taleski, Jean‐Marie Sontag, Astrid Feentje Feiten, Yazi D Ke, Lars M Ittner, Estelle Sontag; "Methyl donor supplementation reduces phospho‐Tau, Fyn and demethylated protein phosphatase 2A levels and mitigates learning and motor deficits in a mouse model of tauopathy"; Neuropathology and applied neurobiology; 2023 Aug

    https://pmc.ncbi.nlm.nih.gov/articles/PMC10947299/

  10. Alex S Carmon, Russell J Amato, Seema M Patel, Shannon W Finks; "Effect of L-Methylfolate Supplementation on Sleep for Patients with Reduced Methylenetetrahydrofolate Reductase Activity"; Journal of dietary supplements; 2024

    https://pubmed.ncbi.nlm.nih.gov/38528721/

  11. Da Hye Kwon, Hee-Jae Cha, Hyesook Lee, Su-Hyun Hong, Cheol Park, Shin-Hyung Park, Gi-Young Kim, Suhkmann Kim, Heui-Soo Kim, Hye-Jin Hwang, Yung Hyun Choi; "Protective Effect of Glutathione against Oxidative Stress-induced Cytotoxicity in RAW 264.7 Macrophages through Activating the Nuclear Factor Erythroid 2-Related Factor-2/Heme Oxygenase-1 Pathway"; Antioxidants (Basel); 2019 Apr

    https://pmc.ncbi.nlm.nih.gov/articles/PMC6523540/

  12. Cara T Hoepner, Roger S McIntyre, George I Papakostas; "Impact of Supplementation and Nutritional Interventions on Pathogenic Processes of Mood Disorders: A Review of the Evidence"; Nutrients; 2021 Feb

    https://pmc.ncbi.nlm.nih.gov/articles/PMC7996954

  13. Boryana Petrova, Adam G Maynard, Peng Wang, Naama Kanarek; "Regulatory mechanisms of one-carbon metabolism enzymes"; The Journal of biological chemistry; 2023 Nov

    https://pmc.ncbi.nlm.nih.gov/articles/PMC10758965/

  14. Gregory S Ducker, Joshua D Rabinowitz; "One-Carbon Metabolism in Health and Disease"; Cell metabolism; 2018 Jan

    https://pmc.ncbi.nlm.nih.gov/articles/PMC5353360/

Katie Stone - Naturopath

About the Author

Katie is a qualified Naturopath (BNatMed) and freelance writer from New Zealand. She specializes in all things health and wellness, particularly dietary supplements and nutrition. Katie is also a dedicated runner and has completed more half-marathons than she can count!

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