Undoubtedly, if you have MTHFR (or even if you don’t) you’ve heard the words folate, folic acid, folinic acid, methylfolate thrown around like a tossed salad…

Speaking of tossed salad, folate is found predominately in uncooked leafy greens – emphasis on ‘uncooked’!

Folic acid on the other hand is mainly found in processed and fortified foods – foods you should be avoiding or at least reducing!

Why is folate so important?

  • Synthesis of nucleic acids (for DNA production and repair and tRNA)
  • Single carbon metabolism (methylation)
  • Interconversion of amino acids (for neurotransmitter production and detoxification)
  • Formation & maturation of RBC, WBC and platelet production

Do you have MTHFR?

If you have a genetic defect with your MTHFR gene then the MTHFR (Methylenetetrahydrofolate reductase) enzyme isn’t going to be able to properly metabolize folate leading to a potential host of problems.

As previously mentioned, folate plays a pivotal role in DNA production and repair, methylation, neurotransmitter production, and red and white blood cell production.  

A genetic polymorphism of C677T can cause the most dysfunction of the MTHFR enzyme with A1298 having a lesser impact on function.

The effects of a MTHFR defect:

  • C677T – homozygous – 70% loss of function
  • C677T – heterozygous – 40% loss of function
  • C677T & A1298C – compound heterozygous – 50% loss of function

For more information on MTHFR, please visit

What’s the difference in folates?

Methylfolate is the most active form of folate produced by the MTHFR enzyme and made in the cytoplasm of ALL cells. Natural forms of methylfolate have an L or 6S in front of the name, if not, they could be a racemic mixture.

What happens if you have too much methylfolate? Methyl trapping!

More is not always better and having too much methylfolate without adequate B12 will block the methionine  cycle. This can set off a cascade of problems including increased homocysteine levels and inhibition of methylation. It also has the potential to increase strand breaks in DNA due to an increase in uracil and decrease in thymidine.

Folinic Acid or 5-formyl tetrahydrofolate is another active form of folate, also known as calcium or sodium folinate. Folinic acid is produced by the SHMT enzyme and must be converted by the MTHFR enzyme into methylfolate.

If your MTHFR enzyme isn’t working then the conversion process to methylfolate may be halted.

Folic Acid – It’s synthetic! It’s possible that your body could process folic acid with a positive outcome but not likely, and certainly not a source to be relied upon.

You would need the MTHFR enzyme & MTHFD1 enzyme to be functioning in order to convert folic acid to 5-methyltetrahydrofolate not to mention nutrients such as B2, B3, B6, B12, Vitamin C, Zinc and normal levels of stomach acid. Most people even if they successfully convert folic acid to the active methylfolate, do not have enough acidity in their gut to properly absorb it.

The dark side of folic acid

Since 1998 the U.S. FDA has required food manufacturers to fortify flour and cereal with folic acid. Not so surprisingly, MTHFR along with autism has been on the rise since foods began being fortified with folic acid.

With today’s modern diets, high intakes of folic acid are common and with only a small percentage making it all the way to the MTHFR enzyme, what happens to the rest?

It becomes unmetabolized folic acid and can decrease natural killer cell activity, mask a B12 deficiency as well as inhibit the MTHFR enzyme. Not exactly something you want to have floating around in your body!


If you are a doctor you need to be specific with your labs and ask “What do you mean when you say ‘folate’ on this lab? Is this folic acid, folinic acid, methylfolate or is it all three?”

It is also worth noting that patients can have adequate serum folate levels but an inability to transport folate into their cells, which is why it is important to test the intracellular folate levels.

How’s your folate status?

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