Methylfolate is found in our bodies, natural folate in foods, and synthetic folic acid in supplements. They are all forms of folate that support various physiological functions in the body.
What is the difference between methylfolate and other forms of folic acid?
The primary difference between methylfolate and natural folate lies in their chemical forms and how the body uses them.
Folate, the form found in plants
Natural folate refers to the various forms of folate found in foods, such as leafy greens and legumes. Natural folate from food sources is essential for overall health and provides a variety of partner nutrients, contributing to a balanced nutritious diet.
After eating this natural type of folate, our bodies have to activate it before it can be put to use. Natural folate from food sources goes through enzymatic conversion in the intestines and liver to become active forms of folate, including methylfolate.
Folic acid, a synthetic form for supplements
Folic acid is laboratory made, as a supplement. The body can modify and use it in place of natural folate from plants, but it does not have the same chemical structure. Dietary folates exist predominantly in the polyglutamyl form (containing several glutamate residues), whereas folic acid — the synthetic vitamin form — is a monoglutamate, containing just one glutamate moiety. In addition, natural folates are reduced molecules, whereas folic acid is fully oxidised.
Methylfolate, the activated form in the body
Methylfolate is the active form of folate, bypassing the need for enzymatic conversion and readily used by the body. It plays a crucial role in various biochemical processes, including DNA synthesis, neurotransmitter synthesis, and methylation reactions.
Methylfolate is the monoglutamyl or fully activated form of folate used in the human body. You may see it go by any of these names on your supplement label: 5-MTHF, 5-methyltetrahydrofolate, L-5-MTHF, 5-methyl-folate or L-methylfolate.
It is directly ready for our cells to use it, without needing any changes by enzymes first. The methylfolate sold as a supplement is laboratory made, but it has the exact same chemical structure as folate that has been processed and activated by enzymes inside the human body.
With high bioavailability – meaning it’s easy to absorb – methylfolate can easily cross cell membranes. It’s popular in nutritional supplements and fortified foods as a bioavailable form of folate. Supplementation with this active form is particularly beneficial for people with impaired methylation processes or those who have difficulty converting folic acid into its active form. It is particularly beneficial for people with impaired folate metabolism or genetic variations that affect the conversion of synthetic folic acid into active folate forms.
Metafolin, a brand of methylfolate
Metafolin is a patented form of L-methylfolate, the active form of folate. It was invented by Merck KGaA, a multinational pharmaceutical company. Metafolin was designed to treat folate deficiency and to provide a bioavailable form of folate supplementation, particularly for people with conditions such as depression, schizophrenia, or epilepsy, who may have difficulty metabolising folic acid into its active form.
Folinic acid (5-Formyltetrahydrofolate)
A partially activated form of folic acid, Folinic acid (5‐formyl tetrahydrofolate) is found naturally in foods, but it is also sometimes synthetically made as a supplement.
Key Points
Folate is natural vitamin B9 found in plants; folic acid is a synthetic, chemically similar substance. Both of these are turned into methylfolate in the liver, which is the form of folate that the body can use.
The benefits of methylfolate over alternative forms of folate
Methylfolate carries out a wide variety of vital processes in the human body. No other form of folate can participate in these processes, as the liver has to convert them into methylfolate first before the body can use them.
Supporting DNA Synthesis and Repair
Methylfolate aids in synthesising and repairing DNA, which is crucial for cell division and growth. By promoting healthy cell replication, it helps prevent DNA damage, lowering the risk of mutations and certain cancers.
Promoting red blood cell Formation: Methylfolate supports the production of red blood cells (erythropoiesis), helping red blood cells to mature in the bone marrow and carry oxygen effectively. This action helps prevent megaloblastic anaemia, characterised by large, immature red blood cells which are bad at carrying oxygen.
Boosting immune function and white blood cells: Methylfolate supports immune function by promoting the proliferation and activity of immune cells such as T cells and natural killer cells. This activity helps maintain a robust immune response, reducing the risk of infections and autoimmune diseases.
Supporting Cognitive Function and Mental Health
Adequate folate levels are have an association with better cognitive performance and lower risk of age-related cognitive decline. Methylfolate is the only form of folate which can cross the blood-brain barrier and directly support mental health. It plays a role in synthesising neurotransmitters like serotonin, dopamine, and norepinephrine, vital for mood regulation and cognitive function. It’s also accepted these days that inadequate methylation plays a significant part in schizophrenia and major depression that doesn’t improve with typical anti-depressants.
Facilitating neural tube formation in pregnancy: Methylfolate contributes to neural tube development during early pregnancy, crucial for preventing neural tube defects like spina bifida and anencephaly in new born babies. This is why eating enough folate before conception and in the first trimester of pregnancy is vital.
Participating in Methylation Reactions
Methylation is crucial for gene expression, cellular signalling, and detoxification processes, supporting overall health and wellness. Methylfolate serves as a coenzyme in methylation reactions, contributing to the methylation of DNA, RNA, proteins, and lipids.
Keeping homocysteine levels down for heart health: Methylfolate participates in converting homocysteine to methionine, an essential amino acid. This activity helps regulate homocysteine levels, lowering the risk of cardiovascular disease.
Key Points
Methylfolate helps the body methylate DNA when creating new cells, including red and white blood cells. This process lowers our risk of cancer. Methylfolate also keeps the brain healthy, supporting mental health and memory formation. It’s essential for detoxing various substances from the body, and keeping the heart and arteries healthy.
What is the right dose of methylfolate?
The right dose of methylfolate can vary depending on individual factors such as age, health status, and specific nutritional needs. However, typical recommended doses for methylfolate supplementation range from 400 to 1,000 micrograms (mcg) per day for most adults.
For people with certain health conditions or genetic variations that affect folate metabolism, higher doses may be necessary under the guidance of a healthcare professional. Pregnant women or those planning pregnancy may require higher doses of methylfolate to support foetal development and prevent neural tube defects.
Key Points
Most adults need 400 mcg to 1000 mcg of methylfolate. Ask your doctor for dosing advice if you are pregnant.
Why is it better to take methylfolate in a vitamin B complex?
Dieticians always tell us to take the B vitamins together in a single supplement. This isn’t just to save money! It’s also better for our bodies that way.
Balanced B Vitamin Intake
B vitamins often work together in metabolic pathways, and imbalances in one B vitamin can affect the function of others. Taking methylfolate as part of a B complex ensures a balanced intake of all essential B vitamins, helping to prevent deficiencies and optimise overall health.
Better Absorption and Utilisation
Some B vitamins, including methylfolate, may have improved absorption and utilisation when taken together with other B vitamins. For example, vitamin B12 is necessary for the activation of methylfolate within the body, and deficiencies in vitamin B12 can impair folate metabolism. By including both methylfolate and vitamin B12 in a B complex, absorption and utilisation of both nutrients may be enhanced.
Synergistic Effects
Methylfolate works synergistically with other B vitamins, such as vitamin B12 (methylcobalamin) and vitamin B6 (pyridoxal-5-phosphate), to support various physiological processes, including energy metabolism, neurotransmitter synthesis, and DNA repair. Combining methylfolate with other B vitamins in a complex can enhance their effectiveness and overall benefits.
Methylation Process: Folate and vitamin B12 are both involved in the methylation process, which is essential for DNA synthesis, neurotransmitter metabolism, and other biochemical reactions in the body. Folate serves as a methyl donor in methylation reactions, while vitamin B12 is necessary for the regeneration of the active form of folate (methyl folate) and the conversion of homocysteine to methionine.
DNA Synthesis: Both folate and vitamin B12 are crucial for DNA synthesis and cell division. Folate provides the methyl groups needed for DNA methylation, while vitamin B12 is necessary for the production of nucleotides, the building blocks of DNA. Deficiencies in either folate or vitamin B12 can lead to impaired DNA synthesis and cell division, resulting in megaloblastic anaemia and other health problems.
Homocysteine Metabolism: Folate and vitamin B12 play key roles in homocysteine metabolism. Elevated levels of homocysteine are associated with an increased risk of cardiovascular disease. Folate helps convert homocysteine to methionine, while vitamin B12 is necessary for the enzyme that catalyses this reaction. Deficiencies in either folate or vitamin B12 can lead to elevated homocysteine levels and an increased risk of cardiovascular problems.
Key Points
It’s best to take methylfolate supplements in a complete vitamin B complex, because it works with the other B vitamins to deliver its benefits. It’s also better absorbed with the other B vitamins.
Is methylfolate safe for everyone?
Methyl folate is generally considered safe for most people when taken at appropriate doses. However, as with any supplement, there are certain considerations to keep in mind.
Medical Conditions
People with certain medical conditions, such as epilepsy, bipolar disorder, or cancer, should use methylfolate supplements with caution and under the guidance of a healthcare professional. methyl folate may interact with certain medications used to treat these conditions, and high doses may not be suitable for everyone.
Pregnancy and Breastfeeding
Methylfolate supplementation is crucial for pregnant women to support foetal development and prevent neural tube defects. However, it’s essential to follow healthcare provider recommendations regarding the appropriate dose, as excessive intake of methyl folate during pregnancy may have adverse effects.
Interactions with Medications
Methylfolate supplements may interact with certain medications, including anticonvulsants, methotrexate, and certain antidepressants. It’s essential to inform healthcare providers about all medications and supplements you’re taking to prevent potential interactions.
Allergic Reactions
While rare, allergic reactions to methylfolate supplements can occur in some people. Symptoms may include rash, itching, swelling, or difficulty breathing. If you experience any adverse reactions after taking methyl folate, discontinue use and consult with a healthcare provider.
Key Points
Methylfolate is safe for most people, but you should consult your doctor before taking it if you have cancer, epilepsy or mental health issues; are pregnant or breastfeeding; take epilepsy medications or antidepressants; or have ever had an allergic reaction to methylfolate.
A word of caution: Methylfolate masking vitamin B12 deficiencies
Folate and vitamin B12 deficiencies can have overlapping symptoms, such as megaloblastic anaemia, fatigue, weakness, and neurological problems. Because folate and vitamin B12 are interconnected in various physiological processes, supplementation with one nutrient can temporarily mask a deficiency in the other.
For example, if someone has a vitamin B12 deficiency and takes a folate supplement, it may improve symptoms related to folate deficiency (such as megaloblastic anaemia) without addressing the underlying vitamin B12 deficiency. This masking effect can delay the diagnosis and treatment of vitamin B12 deficiency, leading to potentially severe neurological complications if left untreated.
This applies to all forms of folate, not just methylfolate.
Therefore, taking a supplement with balanced doses of vitamin B12 as well as folate is a safer option unless you are being guided by a medical professional.
Key Points
Taking folic acid or methylfolate supplements can hide a deficiency in vitamin B12, which is why it’s best to take both together or have a doctor check your status before taking supplements.
