What the MTHFR Is Up with this Fancy Folate?

Learn the difference between these nutrients for your best health.

Posted Mar 16, 2015

dr. peter bongiorno
Source: dr. peter bongiorno

I remember first learning about folic acid maybe 15 years ago in school.  Unless you were a chemist "folic acid" and "folate" were pretty much interchangeable words – except that folate was the form of this B vitamin that occurred naturally in food whereas folic acid was the supplement you would take in a vitamin pill if you needed extra of this nutrient.

In naturopathic medical school, we studied nutrition in great depth. So were taught about the importance of vitamins and food. We learned that folic acid was known to be important for the health of our genetic material (DNA), and also heart and vessel health. Folic acid could also help prevent and treat depression, and even be helpful to minimize the possibility of cervical dysplasia leading to cancer.

Of course, we learned about the most common use of folic acid - in pregnancy. It was well established that pregnant needed extra folic acid to prevent nerve and spinal cord defects in children. By the way, this was probably one of the first wide-scale modern-day admissions by the conventional medical world that a vitamin is useful to prevent a medical problem, even though it took over 25 years from the understanding of this to make it common practice.

Folate Gene Problem?

Despite my nutritionally intensive-naturopathic training, we did not  learn much about this, for the information wasn’t available regarding the difference between folic acid and folate. As happens with medical sciences, we are learning everyday. Now, we have a fuller picture of the folic acid story. It seems that there is a lot more going on than we thought. 

In fact, now we know that ten to fifteen percent of the population have an issue with folic acid. In these people, there is an inability to process folic acid into a useful form that is needed for optimal health.  The gene responsible for this folic acid processing helps to build an enzyme called the “methylenetetrahydrofolate reductase enzyme.” This enzyme is a protein in our body which is responsible for processing the folate into a useful form. The acronym for it is: MTHFR. I think the people who created it must have been laughing all day in the lab when they came up with that one. Work with this acronym however you would like :) .

Anyway, people who have this genetic issue are not able to process folic acid as well as they should, which can allow issues to develop in blood vessels, creating greater risk for heart disease and stroke. It also is linked to greater likelihood of mental health issues like depression, bipolar disorder, and schizophrenia. Also migraines and osteoporosis are concerns too. Of course, pregnancy concerns of nerve tube defects will also be greater.

How To Check for MTHFR Mutations?

Today, it is easy to find out if you have this genetic issue. Just ask your doctor for an MTHFR gene test. It will help you understand if you have this genetic variant (called a mutation) that can lower your ability to utilize folic acid.

Blood tests and buccal (mouth) swab testing are two easy ways to check this in your body. I also recommend testing homocysteine levels and serum or urine methylmalonic acid. The homocysteine level can help you understand if you need more folate, and the methylmalonic acid will help uncover B12 deficiency (even if your serum B12 levels look o.k.)

Regular Folic Acid Supplement versus Methyl-folate: What’s the Difference?

If you are positive for a variant of the MTHFR, it is a pretty easy fix:  get more folic acid. But, the important thing is you pick the right form of folic acid.

“Folic acid” is the synthetic folate we have been giving people for years – and it is well-studied and works pretty well, but only if your genetics help you make the MTHFR enzyme you need to make the methyl-folate form in your body.

If you have genetic mutations for MTHFR, then the best form is the one that already occurs in nature. In general, going with nature is always the best choice!

The word folate comes from the Latin word folium which stands for "leaf." Green vegetables have methyl-folate. This form of folate does not need to be processed by the MTHFR enzyme, so it will get the job done of protecting your vessels, mental health and bones whether you have the ability to process folic acid or not. That is good news for those people with the MTHFR gene mutation.

Cancer Concern with Regular Folic Acid

Another concern of mine for people with the MTHFR mutation is that if they are taking regular folic acid, and cannot process it, then high levels of the synthetic folic acid end up in the blood stream. It seems high levels are associated with cancer. While folic acid may not directly cause cancer to start, it may help cancers that are there grow faster and more effectively. This is interesting, because when folate is properly processed and used in the body, it helps lower cancer rates.

Also, something else we learned in naturopathic medical school is how high levels of folic acid can make it hard to detect low vitamin B12 levels in someone. So, as a caution, it's good to take a little extra B12 if you are taking folate.


1 - I recommend my patients eat green vegetables. These beauties have the natural form of methylfolate, plus a number of other vitamins, healthy fibers, and tons of other phytonutrients that we don’t even know about!

The best sources of methyl-folate are spinach, asparagus, romaine lettuce, turnip greens, mustard greens, collard greens, cauliflower, broccoli, parsley, lentils and beets. Calf’s liver is also a great source – but look for hormone and antibiotic-free animal sources that are naturally raised.

2 – for supplementation, take the methylfolate form: I recommend patients with the genetic MTHFR mutation take about 1000mcg of methylfolate. If a patient also has high homocysteine, I will also prescribe a combination formula that includes vitamin B12, trimethylglycine, and activated forms of vitamin B6 and riboflavin, which will help lower homocysteine.

There is some research that suggests benefit of using super high doses of folate, of up to 5 to 10mg a day to help drugs work in treatment resistant depresion. Outside of this scenario, I prefer to work with lower dosing of 500mcg to 1000mcg.

3 – Stay away from these folate depletors: Smoking, excess alcohol, birth control pills, and stress will all deplete folic acid from your body. Also, poor digestion and low stomach acid will make it harder to absorb your nutrients as well.

about the author: Peter Bongiorno, ND, LAc, is author of How Come They’re Happy and I’m Not? The Complete Natural Guide to Healing Depression for Good. His newest book is Holistic Therapies for Anxiety and Depression by Norton Press. More about Peter can be found at drpeterbongiorno.com and innersourcehealth.com, @drbongiorno and on Facebook.


Deghan MS. Folic acid supplementation promotes mammary tumor progression in a rat model. PLoS One. 2014 Jan 21;9(1):e84635.