I am sure everyone would like a simple answer so they can just buy a product and move on with their lives, but like everything else about MTHFR, this is an individual question.

The very short answer, is both forms will get you there in the end. Don’t worry, I’ve got the much longer answer all ready for you too.

One caveat before we get going – we are entering into unresearched territory here. The effects of 5-LMTHF vs. folinic acid in MTHFR mutants have never actually been studied as a comparison, so the only useful data I can use here in my own clinical experience with myself and my clients. MTHFR is a reasonably new area for scientific research and the research has focused primarily on health risks and disease correlations, as well as basic information about how disease risk changes with folate status, but we are nowhere near the point where we are actually looking at how MTHFR folks feel well.

Fast vs. Slow

In a very real sense, what we are dealing with here, is incredibly fast action, vs. slower steadier action. 5-LMTHF is the active form of folate. As soon as it absorbs, it is useable in a very rapid way. For some MTHFR folks, this is a miracle, but it’s all too much for others. Folinic acid, on the other hand, still has to be converted to the active form, and so has a much slower action because you can only use it as fast as you convert it. For some people, this isn’t enough. For others, it gives the benefits of methylfolate without the scary burst of energy (which can feel like anxiety, heart palpitations, or restlessness if it’s too high.)

how the types of folate interact with the methylation pathway
It is important to understand how different types of folate interact with the methylation pathway in the body

If you look at the diagram above, the enzymes are highlighted in grey. You can see that 5-LMTHF is the end-product of all of this. It doesn’t need to be changed into anything else, because it’s already what we’re after. Folinic acid, on the other hand, still needs the MTHFR enzyme, but bypasses “DHFR Slow,” which only folic acid uses (and you know what I think of folic acid) and the “DHFR Fast” which is used by other forms of natural folate. It’s an efficient way to get good active folate even if your MTHFR is slow, just as long as you don’t have folic acid in your diet slowing everything down.

5-LMTHF vs. folinic acid
5-LMTHF vs. Folic acid: a comparison

Doesn’t Every MTHFR mutant Need The Active Form?

No. Every MTHFR mutant needs good sources of natural folate, but this could be food sources of natural folate (NOT FOODS FORTIFIED WITH FOLIC ACID), folinic acid, or 5-LMTHF. Ultimately, they are all working on solving the same problem they just do so with different levels of efficiency. Here are some quick facts for you.

  • Natural folate, folinic acid, and 5-LMTHF are all useable by MTHFR mutants as long as they don’t have folic acid in their diet.
  • Folic acid makes natural folate and folinic acid less useful because it blocks receptor sites and slows down the methylation pathway.
  • 5-LMTHF is the only form of folate that bypasses the MTHFR enzyme entirely,
  • Natural folate, folinic acid, and 5-LMTHF are all-natural forms of folate.
  • Folinic acid is easier for many MTHFR mutants to tolerate because it is metabolized more slowly.
  • Often, taking folinic acid for several months will help a person who couldn’t tolerate 5-LMTHF to tolerate a low dose.
  • Some MTHFR folks will never be able to tolerate any forms of folate.
  • Because folinic acid metabolizes more slowly, it typically generates fewer side-effects than 5-LMTHF.

Do MTHFR Mutants Need Both Folinic Acid and 5-LMTHF?

The short answer is that we think so, but maybe not.

Here’s why. Folinic acid converts to 5-LMTHF reasonably easily (using the MTHFR enzyme) but 5-LMTHF has to go through a much more complex backward process to convert back to folinic acid. WE think it is important because these two substances feed into different pathways most easily.

In comparison to folinic acid, 5-LMTHF is a powerful antioxidant. Can you tell me which one is the best for people with MTHFR mutations?
In comparison to folinic acid, 5-LMTHF is a powerful antioxidant. Can you tell me which one is the best for people with MTHFR mutations?


  • Bypasses the MTHFR enzyme
  • Supports methylation and production of SAMe
  • Can cross the blood-brain barrier easily
  • Methylates substances like serotonin (to make melatonin), norepinephrine (to make epinephrine)

Folinic Acid

We are nowhere near the point where research is actually asking the question, “How do MTHFR mutants feel well.”

Amy Neuzil, tohealthwiththat.com

Next week we’re going to talk about what to expect when you’re starting to supplement with folate, what symptoms you might see, what is going on in your body an what to do about it.

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