By Richard N. Podell, M.D., MPH www.drpodell.org
Folic Acid along with vitamin B12 play critical roles in human biochemistry. Both are required to transform the amino acid Homocysteine into S-Adenosyl Methionine (SAMe). SAMe, in turn, is one of the body’s main methyl group donors (A methyl group consists of a carbon atom attached to 3 hydrogen atoms=CH3). You have to add methyl groups (methylation) to organic carbon chains in order to build many key biochemicals. For example: serotonin, norepinephrine, dopamine and many more. Folate is also required for DNA synthesis and repair.
Problem: many people get much or most of their folic acid in a synthetic form-added to grains or in standard B complex or multivitamins. But synthetic folic acid is not the active form of folate that we need. To be useful synthetic folic acid to be transformed by an enzyme called MTHFR (methynetetrahydrofolate reductase). BUT, many Americans have inherited one or more defective MTHFR-related genes. These mutations reduce the ability to turn synthetic folic acid into its active form. This active form is called methyl folate. It’s also often called just MTHFR. Please note: a recent study of more than 1000 newborn babies in Wisconsin found that 33% had one defective MTHFR-related gene. Eight percent had two defective genes. A single bad gene (heterozygous) is believed to reduce folic acid activation by about 30%. A double dose (homozygous) can reduce it by 60 or 70%.
Animal studies show clearly that too little active folic acid causes harm in many ways. Logically, we should expect this to be true for humans too. Several alternative medicine- minded websites report that active methylfolate can help people who suffer from many different health problems including autism, chronic fatigue syndrome, depression and other ailments. Unfortunately, there are almost no controlled studies in humans testing this. So, at this point using methylfolate to treat CFS has to be considered as possibly very useful—but, so far, not “proved”.
Good News, Disclaimer and Cautions:
Good News: The folic acid in green leafy vegetables is NOT synthetic. It’s mainly in the form of active methylfolate. So if you eat 5 servings a day of leafy greens (preferably uncooked), you can easily get enough active folate despite having one MTHFR mutation or perhaps even two. But, most Americans don’t regularly eat large clumps of greens. We get much or most of our folic acid in the synthetic form, as a U.S. government mandated additive to grains or from vitamin pills.
Recognizing the potential importance of methyl folate, the FDA has approved two “medical foods”, actually vitamin capsules. These are Metanex and Deplin. Metanex, which I prefer, contains high dose active methylfolate, methyl B12, and vitamin B6. Xymogen and other nutritional companies provide less expensive versions. For example, Xymogen’s product, Methyl Protect. . I do not use Deplin because it contains only methylfolate, but not B12. Taking Folate without B12 has potential dangers.
Fortunately, for most with one or two MTHFR mutations treatment is straight- forward and with very little risk. However, some people, when given methylfolate feel uncomfortably hyper. Therefore, I prefer to start with a low dose multivitamin , such as Multi t/d from Pure Encapsulations. I don’t add high dose products like Metanex of Methyl Product until the low dose is tolerated.
Disclaimer: I have no financial relationship at all with any of the products, labs or websites mentioned in this essay.
Cautions: I am beginning to test all my chronic fatigue syndrome and fibromyalgia patients for the MTHFR mutation. Medicare in my region and New Jersey Blue Cross cover the MTHFR genetic test. But, many insurance companies do not. Without insurance the test is expensive test– in the $300 range for most labs. (Spectracell Labs offers MTHFR at lower cost as an add-on when you do other nutritional testing.) I’ve had some success in treating, but follow up has been too short to form firm conclusions.
Given the potential benefits and minimal risks, I suggest that everyone with any chronic illness-physical or mental have the MTHFR mutation tested. You can call your insurer to learn if it’s covered. Tell them the CPT code is #81291. (CPT codes identify which test is which). Then tell them that your CPT diagnosis is 270.4. That’s the diagnostic code used to justify this test.
Once again, please note: It can be dangerous to supplement with high dose folic acid if there is not also adequate vitamin B12.
Your doctor, might tell you that you don’t need to test for the MTHFR mutation unless your blood level of the amino acid, homocysteine, is abnormally high. Although MTHFR mutations can cause homocysteine to rise, I have a fair number of patients with one or even two MTHFR mutations who have normal or even abnormally low levels of homocysteine.
For some people treatment is more complex, not straight-forward. For example, if MTHFR is abnormal but homocysteine levels are low. Here the biochemistry may be complex and deserves attention by a specialist. A trained medical geneticist should understand the biochemistry, but might decline to treat since we do not yet have double blind studies to prove that treatment works. Dr/ Ben Lynch’s website provides a list of physicians who have taken his courses on MTHFR. His graduates, will likely tend toward the “alternative medicine” side.
Practical Sources for more information:
The most sophisticated website focusing on MTHFR is sponsored by a prominent naturopath named Benjamin Lynch. His site for patients is seekinghealth.com. He has an additional site at MTHFR.net. Consult seekinghealth.com to identify medical clinicians who’ve been certified as having passed Dr. Lynch’s teaching course.
Dr. Lynch His site for health professionals is seekinghealth.org.
Amy Yasko, PhD has a valuable site, specializing in autism and neurological disorders. www. dramyasko.com.
Genetic Genie can download and interpret genetic data obtained through the ancestry and health testing company “23 and me”. This service is free. See geneticgenie.org
A saliva test from “23 and me” costs less than $100. It tests for about a dozen important genes including those relating to folate metabolism. The FDA does not allow them to interpret these gene results—hence the usefulness of Genetic Genie.
For health professionals consider a lab called Doctor’s Data. They can measure the blood levels of intermediates in the folate/methylation cycle. These include the important amino acids: homocysteine, S-Adenosylmethionine, and cystathionine. Doctor’s Data also offer a panel that measures multiple genes relating to the methylation cycle. Click HERE for more information.
Heartfixer.com is another informative site.
Spectracell Labs offers a fairly low price for MTHFR testing as an add on to nutritional testing that’s the main focus of their lab. See Spectracell.com
For biochemistry mavens, here’s a picture of the main methylation pathways: