When Will My L-Methylfolate Start Working?

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You’ve decided to start supplementing with l-methylfolate. Maybe you’ve heard of its mood-boosting capabilities, or you have high homocysteine, or you have been diagnosed with an MTHFR mutation, or perhaps you’re pregnant and understand the critical nature of folate during fetal development. Whatever the reason, now you’re paying attention to how your body feels every day, wondering when you will start to notice the benefits. How long does it take for l-methylfolate to work?

Unfortunately, there are no simple answers to this question…

It really depends on your unique makeup, the health issue you are hoping to address, and how deficient your body was before starting your new regimen. Some people feel a difference within minutes after taking a methylfolate supplement. Others start to notice a shift after a few weeks. You may also feel nothing at all, ever. Some nutritional deficiencies, and recoveries, may only be noted by a blood test.

Is My L–Methylfolate Supplement Working?

A supplement has “worked” when your body has absorbed it, converted it to a usable form (if necessary), and your circulating levels for that nutrient are within the normal range. Since methylfolate is already in a usable form, how long it takes for l-methylfolate to “work” is all about absorption and circulation.

Supplements are not meant to treat any disease conditions or change the way you think or feel. However, your nutritional status (whether you are deficient/insufficient in certain nutrients) can impact both mental and physical health. Supplements can help to correct a nutritional deficiency and maintain nutritional balance. You may notice that you feel better in your body and mind once you have reached, and are maintaining, healthy levels of methylfolate.

If you and your doctor have come to the decision that a high-potency, 15 mg dose of methylfolate is a good option for you, you two are also the experts on whether or not the supplementation is “working” for your body and mind. Keep checking in and be sure to follow their recommended protocols carefully.

It’s important to note that taking one capsule, or even a capsule a day for a couple of weeks, may not be long enough to reach and maintain normal circulating levels. For example, many l-methylfolate studies take baseline measurements of participants and then do not assess them again until they have completed 6, 8, 10, or even 12 weeks of regular supplementation [1-3].

When should I talk to my doctor?

If you have been taking a supplement regularly for two months or more and feel no difference in your mood, energy level, or general health, a blood test from your doctor can help to determine whether your supplement is being absorbed and circulating in your body efficiently. If you’re wondering how long it takes for l-methylfolate to work based feelings, it is possible for a supplement to correct your deficiency without changing the way you feel.

While l-methylfolate’s safety profile is similar to a placebo [4], some individuals are sensitive to high levels of methylfolate and may feel adverse effects. Stop taking the supplement immediately, and talk to your doctor if you feel negative or uncomfortable symptoms after taking l-methylfolate.

Why Isn’t My Supplement Working?

If your blood work shows you have enough methylfolate but are deficient in other nutrients, your body may not be using methylfolate effectively (see “cofactors” below).

If a blood test shows your supplement is not helping to correct a deficiency or insufficiency, you may be having issues with absorption. Below are some reasons why this may be happening.

Forms of Folate

Folate is a broad term that encompasses many forms of vitamin B9. L-Methylfolate is, specifically, the activated form of folate usable by the body. It is NOT the same as folic acid.

Folic acid is an inactive, synthetic form of folate that must be converted to l-methylfolate by an enzyme in the body called methylenetetrahydrofolate reductase, or MTHFR. The problem is that many people do not make efficient levels of this enzyme due to genetic variations. This can cause folate deficiency and high homocysteine, even when the diet appears to contain enough folic acid for a healthy individual.

Check your supplement for the right form of l-methylfolate. It should be named specifically as L-Methylfolate, L-Methylfolate calcium or glucosamine salt, L-5-MTHF, L-5-methyltetrahydrofolate, or (6S)-5-methyltetrahydrofolate.

L- and 6(S)- indicate biologically active forms of methylfolate (helpful). D- and 6(R)- indicate non-biologically active forms of methylfolate (not helpful). If your supplement just says Methylfolate or 5-MTHF and does not specify L-methylfolate or 6(S)-methylfolate (or does not contain brand names like Quatrefolic or Metafolin), this is grounds for skepticism over the quality of your source.

If you have high homocysteine and/or have been diagnosed with an MTHFR mutation, be sure to avoid folic acid-containing supplements and take only l-methylfolate.

Quality vs. Savings ($)

Where did you get your supplements? The grocery store or your doctor?

If your supplements were “a great deal” compared to other brands, they may contain cheaper, less bioavailable forms, lower-quality ingredients, or ingredients that do not match the claims on the label. How long it takes for l-methylfolate to work maybe “never” if you’re taking a poor quality product with low nutritive value. As such, it is important to only purchase supplements from reputable dealers whom you trust.

Would you rather spend less and see little to no result? Or, spend slightly more and see the changes you hope for? If you don’t have a go-to brand you trust yet, ask an expert. For the purest supplements with the highest-quality ingredients, naturopathic physicians are a great source of recommendations.


Synthetic fillers, anti-caking agents, coatings, and other elements can also interfere with absorption. Look for a brand that states outright that they do not add these ingredients and check the ingredient list for purity.

Unique Interferences

Do you have any health issues that could be interfering with absorption? Crohn’s disease, chronic diarrhea, dysbiosis, leaky gut, and other issues of the gastrointestinal system can interfere with proper nutrient absorption.

Some specific medications can interfere with folate levels and/or absorption. These include some birth control medications, anticonvulsants, Methotrexate, and cholesterol-reducing medications. You can ask your doctor or pharmacist, or look up these interactions by searching the name of your medication.


Methylfolate does not work alone in the body. It requires the aid of several other nutrients to fulfill its functions. Some of the most important cofactors for homocysteine maintenance and the production and metabolism of neurotransmitters (serotonin, dopamine, etc.) are vitamin B12, vitamin B6, and magnesium. MethylPro offers a methylfolate supplement that includes its cofactors. MethylPro also makes a B-complex supplement containing varying doses of methylfolate if you are interested in an all-in-one option.

A B12 deficiency and a folate deficiency can be hard to distinguish from one another. Make sure you are getting both if you think a deficiency of either is possible. Vitamin B12 can also be supplemented in its active, methylated form, as methylcobalamin. Look for that specific name on your supplement facts.

How long do I need to take methylfolate for?

Eating a single salad does not negate the importance of a daily balanced diet. Similarly, taking one capsule of a nutritional supplement cannot improve your health in a meaningful way. Using a supplement to boost your nutritional health takes time, regularity, and patience. As such, please be consistent when you’re waiting to find out how long it takes for l-methylfolate to work.

Some people know exactly why they are folate-deficient. Perhaps it was a dietary choice, like veganism or vegetarianism, that led to a point of B-vitamin deficiency. Perhaps a medication like Methotrexate was interfering with folate absorption, and now the prescription has ended. For these people, supplementation may help them recover from deficiency, and then may no longer be necessary due to a well-fortified diet.

Those of us that with an MTHFR variation, however, may need to take methylfolate supplements for life. If folic acid is unsuitable for your body, and food folate is also difficult to absorb and process, it can be really difficult to get enough active methylfolate in the circulation without the addition of an l-methylfolate supplement.

As a water-soluble vitamin, methylfolate is highly safe. Excess amounts of this nutrient are excreted through the urine. It does not accumulate in the body the way a fat-soluble vitamin or mineral supplement can.

Once you have found the right time of day for your supplement (e.g. morning for all your energy-boosting B vitamins, bedtime for relaxing with magnesium), make taking the supplement a part of your routine. Expect it to stay a part of your routine unless your doctor has recommended otherwise.

Consider a Supplement Subscription

Once you have adjusted to regular supplementation with methylfolate, you will likely feel the difference when you skip or miss a day’s supplement. The good news is that we have a service available that can reduce these occurrences. With the launch of our new website in June 2024, MethylPro is offering a “Subscribe and Save” option at checkout. You will save 10% on your first subscription order and 5% off each subsequent delivery in that subscription.

Rather than keeping track of how many capsules you have left in the bottle, and trying to factor in transit times before ordering your next shipment, we can keep track for you. If you have a bottle with 30 capsules, and you take 1 a day, you can have a bottle delivered automatically once a month. Ninety capsules? Schedule your delivery once every three months.

Maybe you worry about how often you travel. Maybe you worry you’ll start accidentally stockpiling if you skip a few days here and there. MethylPro now offers a “skip” feature, so you can skip one order and get back on track for the next delivery. You can also cancel any subscription, without penalty.

We already have so much to keep track of these days, “remember to order methylfolate” can be one less item on your to-do list. No gimmicks, just a helpful feature to make sure you never miss a supplement because you forgot to make an order.

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  1. https://www.sciencedirect.com/science/article/abs/pii/S0165032700001531
  2. https://www.sciencedirect.com/science/article/abs/pii/S2405457723012329
  3. https://journals.sagepub.com/doi/abs/10.1177/070674371205700703
  4. https://europepmc.org/article/med/31833826

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