The Great Folate Debate

Since 1959 it has been known that folic acid deficiency results in the inability to degrade formiminoglutamic acid (FIGLU), so that FIGLU accumulates in your body and is excreted in your urine. The Metabolic Analysis Profile test (MAP test) uses this principle to assess your folic acid sufficiency. Your FILGU levels are measured and high levels suggest a need to use low dose folate and folic acid support.

It is important to use both folic acid and folate supplementation for several reasons. The first is the pathway that involves MTHFS, an enzyme in the methylation pathway. MTHFS functions in the folate cycle, where it catalyzes a reaction that turns formyl tetrahydrofolate, or folinic acid, into tetrahydrofolate (THF), or what you ordinarily think of as folic acid.

MTHFS also impacts the formation of guanine and adenine, two purines that are necessary for DNA and RNA formation, the formation of fast turnover cells like blood cells or GI tract lining, and wound healing. If you have a mutation that reduces MTHFS activity, folinic acid can build up to high levels, your synthesis of guanine and adenine is reduced, and your tetrahydrofolate level is also decreased.

Dr. Amy Yasko’s program uses low dose folinic acid to prevent its build up, adds guanine and adenine to support DNA and RNA production, and uses low dose folic acid along with probiotics as a secondary way to make THF. In this way, the impact of any possible MTHFS mutation is bypassed, even if you do not have data regarding this gene.

Dr. Amy wants to consider all aspects of a particular pathway when adding support. She chooses to add only low dose folinic acid to keep the levels of folinic acid from climbing, which could happen if you are adding high dose folinic acid and have a MTHFS mutation. She adds guanine and adenine to supply purines in case the pathway for their formation is not fully functional. She adds low dose folic acid to have a secondary route for making THF, a route that also consumes excess glutamate.

The rationale behind adding low dose 5 methyl THF also is that the way to bypass an MTHFR C677T mutation is with 5 methyl THF. No amount of folinic acid, folate, or folic acid is going to bypass a MTHFR C677T mutation. Folate will not bypass MTHFR. 5 methyl THF is the only way to bypass MTHFR C677T.

Using high dose 5 methyl THF at the beginning of a treatment for MTHFR + can trigger more detox than you can handle, especially if you are an adult. You may need to supply your body with nutritional groundwork and ease into 5 methyl THF administration.

Folate is basically a chain of glutamates. The difference between folic acid and folate is the stability and the length of their glutamate chains. So, if you are MTHFR C677T++ and you take high dose folate, you potentially have a chain of unused glutamate molecules left in your body. You cannot process it efficiently to 5 methyl THF because of your mutation. You run the risk of folate breaking down to release glutamate into your system.

Folic acid has a shorter glutamate chain than folate. Folic acid is also more stable, so it is less likely to break down into glutamate. Dr. Amy uses only a tiny bit of folic acid, to allow FIGLU to convert into glutamic acid. Most of the folate that is used for Dr. Amy’s program is 5 methyl THF, with some low dose folinic acid.

Dr. Amy has specific reasons for the choices she makes in terms of supplements and the forms that she uses. The RDA for folate/folic acid is 300 micrograms for a child that is 1 year old, and up to 1,000 micrograms daily for an individual 19 years of age or older. Thus the 15 to 40 micrograms used for her program is not an issue, especially since the body does need some folate and folic acid aside from the need for 5 methyl THF and folinic. To put this in an easily understandable perspective, a bowl of cheerios has 400 micrograms of folic acid, as compared to the 15 to 40 micrograms used in her program.

High levels of the enzyme urocanase will also increase FIGLU. Urocanase is produced by certain bacteria, including Pseudomonas, so consider stool testing when high FIGLU is noted on a MAP. Urocanase is limited by succinate. Be sure that succinate levels on a MAP test are in balance, because a lack of succinate combined with bacterial increases in urocanase can be factors in high FIGLU as opposed to a need for folate.

This information has been excerpted from Dr. Amy’s online book Feel Good Biochemistry, that can be found at

Dr. Mullan would like to invite you to her Open Forum which is held on Tuesday night at 5:00 PM Pacific Time (8:00 PM Eastern Daylight Time, 7:00 PM Central, 6:00 PM Mountain) in order to answer your questions and introduce you to her work. You may be checking her out to see if you would like to consult her. Or you may not have the option of working with her, but would still like to get her information.

The call in number is (605) 562-3140, and the access code is 691392#.

When you hear Dr. Mullan come on the line, press *6 to get into the question and answer line if you have a question.

This program is not recorded. International call in numbers are linked here.

Thank you for your interest in Dr Mullan’s work.

Nancy Mullan MD

Author, lecturer, clinician
Dr. Nancy Mullan is best known for her natural treatment of chronic illness, including Autism Spectrum Disorders, Lyme and MTHFR+.

2829 Burbank Blvd., Suite 202, Burbank, CA 91505
T: (818) 954-9267 – F: (818) 954-0620


About Nancy Mullan, MD

Some people call Dr. Nancy Mullan the MTHFR genetic medicine expert. Dr. Mullan works with people who are struggling with chronic disease or other significant illness, who are willing to use diet and genetics-based nutritional supplementation, and who want to increase wellbeing and energy, enhance immunity, lift mood, fine-tune genetic function, and get their lives back. Dr. Mullan has studied at a number of exceptional institutions: the University of Pennsylvania, Tufts University School of Medicine, and the University of Chicago Hospitals and Clinics. She excels at integrating the results of biochemical and genetic testing into sustained clinical improvement for you. She has succeeded with patients who confounded the specialists at Massachusetts General Hospital, the Mayo Clinic, the Cleveland Clinic, Stanford, and many well-known integrative medical doctors. When recommending her, her patients say, “This is the woman you need to talk to. She really knows how to handle tough clinical problems.” Dr. Mullan's specialty areas are MTHFR+, methylation genetics, and genetics-based nutritional supplementation. Within this context, she most often works with Chronic Fatigue Syndrome, Lyme Disease, Psychiatric Disorders, Autism Spectrum Disorders, Women’s Health Issues, Thyroid Disorder, Gastrointestinal Disorder, and Heavy Metal Toxicity.
This entry was posted in Uncategorized. Bookmark the permalink.

Leave a Reply

Please log in using one of these methods to post your comment: Logo

You are commenting using your account. Log Out /  Change )

Google+ photo

You are commenting using your Google+ account. Log Out /  Change )

Twitter picture

You are commenting using your Twitter account. Log Out /  Change )

Facebook photo

You are commenting using your Facebook account. Log Out /  Change )


Connecting to %s