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The MTHFR Mutation: Important for CFS-ME? Important for everything?

  [ 22 votes ]   [ 5 Comments ]
By Richard N. Podell, M.D., MPH • www.ProHealth.com • November 20, 2014


The MTHFR Mutation: Important for CFS-ME? Important for everything?
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:

5-CH3THF= 5 methyltetrahydrofolate=methylfolate, B12 is vitamin B12
 
MTHFR=methylenetetrahydrofolate reductase. This is the key enzyme for which mutation is common, and which, when mutated reduces the ability for synthetic folic acid to be transformed into the active methylfolate
 
SAM=S-Adenosyl Methionine SAH=S Adenosyl Homocysteine
 
CBS is Cystathionine Beta Synthase



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Article Comments Post a Comment

This article
Posted by: IanH
Nov 20, 2014
would have been more helpful (and convincing) if it had identified which polymorphisms of the MTHFR gene are responsible for the "poor conversion" of folic acid to MTHF.

I have not seen a single article which shows which of the many SNps is responsible.

We know that homocysteine levels are significantly affected by these SNPs and the supplementation with folic acid but we do not know whether it is the folic acid that is inducing this but actually more likely to be SNPs in other genes/enzymes of the folate pathway. I do not know of any paper which says these problems are averted by taking methylfolate. If someone could point me to the research if it is available.

I take MTHF rather than folic acid but I am still not convinced it is necessary.
Reply Reply

 
Which SNP is responsible for the "poor conversion"
Posted by: ljimbo42
Nov 28, 2014
Hi Ian- The SNP that is primarily responsible for interfering with the folic acid to methylfolate conversion is the C677T. This is the one that is being referred to in the article. As was said in the article, one SNP reduces the conversion of folic acid to methylfolate by 30% and two SNP's reduce the conversion by 60-70%. Then you add to that a higher demand for methylfolate from stress, poor diet, infections, type A personailties etc. You can end up with a methylfolate deficiency. Then add years or decades to that deficiency. What would say a 20 or 30 year folate deficiency do to one's body?

 

 
Mthfr mutation
Posted by: remacg
Dec 3, 2014
If no mthfr mutations come up with testing, is supplementing with b12 , b6 and folate as helpful?

 


Anemia
Posted by: Katwilm
Jan 27, 2015
Every time I've ever had my iron blood levels checked I've been on the low side and I don't tolerate taking iron too well. I wondered if having this mutation might cause someone to be mildly anemic.
Reply Reply

CFS, FBM, MTHFR mutation
Posted by: artbykris
May 29, 2015
As I write this I am in bed with the most severe fatigue I have ever had. I have UC and psoriatic arthritis, degenerative disk disease,facet arthritis in lower spine. But my biggest issue has been widespread pain since 2008. Went to a rheumy...he simply passed me back to my gastro saying I needed Humira. No insurance, and I am not sure I would do it anyway. D.O. told me this is just "aging" and prescribed cymbalta. I have tried cymbalta twice and it makes me feel insane. Literally. A few years back I went to an integrative practitioner who did about $10,000 in blood tests. One test was for MTHFR mutation and I was positive. She just said "take folate." I cannot begin to describe how this has impacted my life. Though I have no diagnosis,I have no doubt that I have CFS and FMS. This past week has been horrible. I literally can do nothing but sleep. I am 54 and feel like I am 84. My life is nothing. SO my question is, I want to try the Methyl Protect. But I am afraid it could flare my colon, and I am in a mild flare now. I need help. I trust no one anymore. No one listens. I can't start the round of doctors all over again...can't afford it. Help?
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