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Vitamin B9 (5-Methyltetrahydrofolate)
Ingredients/Vitamin/Vitamin B9 (5-Methyltetrahydrofolate)

Vitamin B9 (5-Methyltetrahydrofolate).

Strength pending.The research strength is not set yet.

It supplies folate in the form your blood already carries, feeding the reaction that turns homocysteine back into methionine and keeping cell division supplied.

VBVitamin
Vitamin B9 (5-Methyltetrahydrofolate)IngredientMD
Category
Vitamin

What Vitamin B9 (5-Methyltetrahydrofolate) is, and what it does.

Does it work
Suits anyone planning a pregnancy, people eating few leafy greens or pulses, and people who carry the slower MTHFR variant and want folate further downstream.
How much to take
No daily amount is on record here. Start with what a prenatal or B complex already provides, and keep B12 alongside it.
Time to feel it
Plasma folate moves within days, while red cell folate takes a couple of months to catch up. This is a marker change rather than a sensation.
The first dose
Day one is quiet. The molecule enters the folate pool directly and starts feeding methionine synthase. The work is biochemical from the first dose.
With regular use
Over weeks, red cell folate rises and homocysteine settles in people who were running low. Fast-turnover tissue like gut lining and marrow draws on it first.
How well tolerated
Well tolerated. The thing to get right is B12: folate can normalise the red cell picture while B12 status stays low, so pair them and check with a clinician.
How it feels
No direct sensation for most people. Where anything shows up, it's in bloodwork over the following couple of months.
The overlooked benefit
It's the folate form that crosses into the brain in meaningful quantity, taken up by a receptor at the choroid plexus rather than diffusing in.

The proof, claim by claim.

These words describe the research, not the molecule's worth. Research strength is how much work stands behind one claim, and it is never a product score.

  • folate statusMeta-analysis
  • homocysteine already in the normal rangeMeta-analysis
  • folate status before and during early pregnancyMeta-analysis
  • red cell folate response compared with folic acidRandomised trial
  • folate handling in carriers of the MTHFR C677T variantRandomised trial
PubMedCochraneClinicalTrials.govNIH ODSSUPP.AILabs test. IngredientMD verifies.PubMedCochraneClinicalTrials.govNIH ODSSUPP.AILabs test. IngredientMD verifies.
Pairs well with9 on file

Why these belong in the same formula. Each row says what the basis is, from settled biochemistry through to a trial that measured the pair.

Vitamin B9 (5-Methyltetrahydrofolate) + Vitamin B12Established biochemistry of the methionine synthase reaction

5-MTHF donates its methyl group to homocysteine only through methionine synthase, and that enzyme needs methylcobalamin as its cofactor. Without adequate B12 the methyl group stays stuck on folate, a state described as the methyl trap. High folate intake can also normalise the blood picture of B12 deficiency while nerve involvement continues, which is why the two are usually assessed together.

Vitamin B9 (5-Methyltetrahydrofolate) + Vitamin B6 (Pyridoxine)Established biochemistry of the transsulfuration pathway

5-MTHF clears homocysteine by remethylating it back to methionine. P5P, the active form of B6, drives the other exit route, cystathionine beta-synthase, which sends homocysteine down to cysteine. The two routes handle different loads, so B-complex formulas usually carry both.

Vitamin B9 (5-Methyltetrahydrofolate) + Vitamin B2 (Riboflavin)Established cofactor relationship at MTHFR

MTHFR is a flavoprotein and holds FAD, made from riboflavin, as its cofactor. That matters mostly for people converting folic acid or dietary folate into 5-MTHF, since supplemental 5-MTHF is already past that step. Riboflavin status still shapes how the wider folate cycle runs.

Vitamin B9 (5-Methyltetrahydrofolate) + TrimethylglycineEstablished parallel remethylation route

Betaine remethylates homocysteine through betaine-homocysteine methyltransferase, a route that runs in liver and kidney and does not need folate or B12. It works alongside the 5-MTHF route rather than through it. Formulas aimed at methylation support commonly pair them for that reason.

Vitamin B9 (5-Methyltetrahydrofolate) + Folic AcidEstablished competition at the same transporters and binding proteins

Folic acid is a synthetic oxidised form that must pass through dihydrofolate reductase before it becomes usable, while 5-MTHF is already the circulating form. Both use the reduced folate carrier and folate receptors, so they compete for uptake. Unmetabolised folic acid appearing in blood at higher intakes reflects the limited capacity of that reduction step.

Vitamin B9 (5-Methyltetrahydrofolate) + ZincEstablished interaction at intestinal folate hydrolysis

Intestinal folate conjugase, which strips the polyglutamate tail off dietary folates, is a zinc-dependent enzyme. Supplemental 5-MTHF arrives as a monoglutamate and skips that step, so the dependency applies mainly to food folate. Very high folate intakes have also been reported to interfere with zinc absorption, though findings are inconsistent.

Vitamin B9 (5-Methyltetrahydrofolate) + CholineEstablished shared methyl-group economy

Choline is oxidised to betaine and feeds the same methyl pool that 5-MTHF supplies. When folate intake is low the body draws harder on choline, and the same is true in the other direction. Requirements for one shift with the status of the other.

Vitamin B9 (5-Methyltetrahydrofolate) + MethylfolateNaming overlap rather than a distinct partner

Methylfolate and 5-methyltetrahydrofolate name the same molecule, sold under salt forms such as calcium L-5-MTHF and glucosamine L-5-MTHF. Stacking both means doubling one nutrient without knowing it. Anyone combining products should add the labelled amounts together.

Vitamin B9 (5-Methyltetrahydrofolate) + Vitamin CEstablished chemical stabilisation of reduced folates

Reduced folates oxidise readily in air, light and acid. Ascorbate is a common antioxidant partner in folate formulations and in the assay chemistry used to measure serum folate. The pairing is formulation convention rather than a claimed clinical effect.

Who should be cautious

Nothing specific on file for Vitamin B9 (5-Methyltetrahydrofolate). Match the label to the daily amount above, and tell your doctor what you take.

Not medical advice. Show the label to your pharmacist.

What Vitamin B9 (5-Methyltetrahydrofolate) actually does.

Established

It donates a methyl group to an enzyme that turns homocysteine into methionine, while also regenerating the base folate form for the rest of the folate cycle.

Established

The methionine made in that step becomes the body's main methyl-group donor, used for DNA, protein and neurotransmitter modification.

Established

Because this form skips two enzyme steps that folic acid must go through, it bypasses a common genetic variation that can slow that conversion in some people.

Established

The folate this form regenerates feeds enzymes needed for building DNA building blocks, which is why folate status shows up first in fast-dividing tissue like bone marrow and gut lining.

Made in a lab, 5 steps on record

Where Vitamin B9 (5-Methyltetrahydrofolate) comes from.

Made in a factory, not extracted from plants. The point of the manufacturing is to hand the body folate in the exact form it already uses, so nothing has to be converted first.

Chemically synthesised. The molecule is identical to the one a plant or an animal makes, and building it deliberately means a known purity, a fixed dose and no crop contaminants. For several nutrients this is the only route that reaches a usable amount.

Starts as
Pterin and para-aminobenzoylglutamate building blocks

Commercial production starts from petrochemical and fermentation-derived intermediates that assemble the pteridine ring and the glutamate tail.

Converted by
Reduction and methylation

Folic acid is chemically reduced to tetrahydrofolate, then formylated or methylated to reach the 5-methyl substitution.

Purified by
Diastereomer resolution

Manufacturers separate the biologically usable (6S) diastereomer from the (6R) form, since only one is used by human enzymes.

Ends up as
Salt crystallisation

The resolved acid is crystallised with calcium or glucosamine to give a solid stable enough for tableting and capsules.

Standardised to
Assay to labelled potency

Material is assayed by HPLC and blended to a declared amount, usually expressed as dietary folate equivalents.

Getting Vitamin B9 (5-Methyltetrahydrofolate) from food.

The whole-food sources on file. A supplement closes the gap, it does not replace dinner.

Spinach, rawLentils, cookedChickpeas, cookedAsparagus, cookedAvocado

A gram-for-gram figure (how much of each you would eat to match a dose) will appear here once it is sourced and reviewed. This page will not print a number it cannot cite.

The forms it comes in.

Calcium L-5-MTHF, Metafolin, Levomefolate calciumThe calcium salt of the L (6S) diastereomer, supplied as a crystalline powder that is sensitive to moisture.Fits The most widely used form in multivitamins and prenatal formulas, with the longest record of commercial use.Trade-off Hygroscopic and sensitive to light and heat, so it needs protective packaging and often an antioxidant carrier.
D,L-5-MTHFA mixture of the natural (6S) and unnatural (6R) diastereomers in roughly equal parts.Fits Appears mainly in older or lower-cost material streams.Trade-off Only the (6S) half is biologically active, and the (6R) half circulates without being used, so the labelled amount overstates what the body can work with.
5-formyltetrahydrofolate, leucovorinA different reduced folate, formyl rather than methyl substituted, which enters the folate pool one step upstream of 5-MTHF.Fits Chosen where a non-methyl reduced folate is wanted, and used in clinical medicine as a rescue agent.Trade-off Needs conversion to reach the methyl form, and it is a distinct nutrient rather than an equivalent swap.
What the strongest studies found

The essence, in one line each.

  1. An aptamer-based electrochemical and colorimetric sensor detected 5-methyltetrahydrofolate selectively, which is an analytical method development rather than a health finding.In vitro study. Xu Q et al., 2025 (Biosensors & bioelectronics). PMID 40886437 ↗
  2. A dual isotope design was used to measure how much folate from brewer's yeast reaches circulation compared with a reference dose, addressing bioavailability rather than any clinical outcome.Randomised trial. Weber N et al., 2026 (Molecular Nutrition & Food Research). PMID 41954190 ↗

These are the studies our verdict leans on, chosen from the 2 we read for Vitamin B9 (5-Methyltetrahydrofolate). The full linked list is below.

FDA Disclaimer: These statements have not been evaluated by the Food and Drug Administration. This information is for educational purposes only and is not intended to diagnose, treat, cure, or prevent any disease. Consult your healthcare provider before starting any supplement regimen.