Tuesday, September 10, 2013

Methylation and MTHFR

What is Methylation

Simply put, methylation is a chemical reaction that occurs in every cell and tissue in our body.  Chemically speaking, methylation is the process of adding methyl groups to a molecule.  (A methyl group is a chemical structure made of one carbon and three hydrogen atoms.)  Since methyl groups are chemically inert, adding them to a protein (the process of methylation) changes how that protein reacts to other substances in the body, thus affecting how that protein behaves.  Enzymes, hormones and even genes are proteins and the process of methylation affects them all.

In some way, methylation of proteins helps the body detoxify.  For example, the methylation process helps convert the toxic amino acid (homocysteine) into a beneficial amino acid (methionine).  If your body cannot methylate properly, toxins build up in your bloodstream and will eventually cause disease. 

Another role of methylation is to help the enzymes in our bodies work efficiently.  Enzymes are proteins that act like switches for chemical reactions-they initiate very important processes in every cell and tissue.  In a similar way, methylation affects our genes, which are also made up of proteins.  In fact, methylation can turn genes on and off, which can be good or bad for our health, depending on the gene.

Some nutrients affect the process of methylation quite dramatically-methyl donors (nutrients like folate and choline) actually donate methyl groups to proteins and methylating factors (nutrients like vitamin B12 and zinc) helps this process along by monitoring specific methylation reactions.  how well your body "can methylate" is important to your overall health.

What is MTHFR and How is it Related to Methylation

MTHFR (methylenetetrahydrofolate reductase) is an enzyme that converts folic acid into usable form that our bodies need.  It is a key enzyme in an important detoxification reaction in the body-one that converts homocysteine (toxic) to methionine (benign).  If this enzyme is impaired, this detoxification reaction is impaired, leading to high homocysteine blood levels.  homocysteine is abrasive to blood vessels, essentially scratching them, leaving damage that causes heart attacks, stroke, dementia and a host of other problems.

Additionally, when the enzyme MTHFR is impaired, other methylation reactions are compromised.  Some of these methylation reactions affect neurotransmitters, which is why impaired MTHFR activity is linked with depression.  Inefficiency of the MTHFR enzyme is also linked to migraines, autism, fertility, cancer and birth defects, all of which depend on proper methylation.

High levels of homocysteine can be attributed to many conditions such as: 
*  The condition can lead to high rates of dementia /Alzheimer`s due to a decrease in vitamin B-12. 
*  High homocysteinemia can lead to coronary artery disease, common carotid atherosclerosis other Vascular Diseases.
*  Complications in Pregnancy Due To Neural Tube Defects. 
*  Atherosclerosis
*  Rheumatoid Arthritis
*  Downs Syndrome
*  Alcoholism
*  Osteoporosis
*  Neuropsychiatric Disorders
*  Non Insulin Dependant Diabetes
*  Early Pregnancy Loss
*  Spontaneous Abortion (Viable Fetus)
*  Placental Abruption, Low Birth Weight

What is the MTHFR?

There is a gene called the MTHFR gene that basically controls how well this enzyme works.  A simple blood test can tell you if you have variant copies of this gene.

There are over 50 known MTHFR variants, but the two prime variants are called 677 and 1298, the numbers refer to their location on the gene.  The routine lab test for MTHFR variant only reports on 677 and 1298 as these are the most studied.

The 677 variant is associated  with early heart disease and stroke and the 1298 variant with a variety chronic illnesses.  The MTHFR is reported out as heterozygous or homozygous.  If you are heterozygous you have one affected gene and one normal gene (could have come from either parent).    The MTHFR enzyme will run at about 55% to 70% efficiency compared to a normal MTHFR enzyme.  If you are homozygous then enzyme efficiency drops down to 7% to 10% of normal, which of course makes a huge difference."  Emmalin is homozygous as am I.  She got one copy from her father and one copy from me, just as I received one from each of my parents.

"The worst combination is 677/1298 in which you are heterozygous to both anomalies.  Many chronic illnesses are linked to this anomaly.  98% of autistic children have an MTHFR anomaly.  Fibromyalgia, irritable bowel syndrome, migraines, are all conditions associated with MTHFR anomaly." 
"MTHFR can make you susceptible to illness because the pathway is the primary source of glutathione production in the body.  Glutathione is the body's primary antioxidant and detoxifier.  People with MTHFR anomalies usually have low glutathione, which makes them more susceptible to stress and less tolerant to toxins."  
"As we age MTHFR problems get much worse due to the accumulation of toxins and the cumulative effect of oxidative stress, which ages our bodies."

What kind of symptoms are associated with the MTHFR gene defects?

There are many different symptoms someone with one or both gene mutations might encounter.  Not everyone has the same set of symptoms because there are many other genetic and environmental differences that complicate health.  But if you boil it down, there is a key systemic problem that comes from low methylation and it causes three different symptom areas. 

Systemic problem:  Homocysteine levels are too high due to the fact that not enough Methylfolate is available to convert the Homocysteine into Methionine, SAMe and Glutathione.  Think of Methylfolate (L-MTHF or 5-MTHF) as the wizard changing the bad guy (Homocysteine) into good guys (SAMe and Glutathione).

Three symptom areas:

    1.  Central Nervous System disorders - some of these come from Homocysteine not getting converted into SAMe.  SAMe is responsible for creating Serotonin, Dopamine, and Norepinephrine (neurotransmitters responsible for mood, motivation, and to some degree energy levels - if these are low, then Depression is often the result, but even aggression and alcoholism are symptoms sometimes found in men).  Pregnant women may encounter extreme Post-partum depression.  Also, things like Fibromyalgia, Chronic Fatigue Syndrome, Migraines, IBS (Irritable Bowel Syndrome), Memory loss with Alzheimer's and Dementia and other psychiatric problems can be tied to this issue (OCD, Bipolar, Schizophrenia, and more).  These challenges are typically more related to the 1298 gene mutation.  A very recent clinical trial (not even published yet) was done by Dr. Fava (July, 2011) showed that giving L-Methylfolate (Metafolin) found in the prescription 'medical food', Deplin, was as effective as the top anti-depressant drugs available today (and without all the side effects).

   2.  Cardiovascular problems often occur when Homocysteine levels in the body are too high.  Heart attack, Stroke, Blood clots, Peripheral neuropathy, Anemia even Miscarriages and Congenital birth defects can be related to this issue among others.  These problems are typically more related to the 677 gene mutation, but the worst is for a person who has one 677 variant and one 1298 variant.

    3.  Environmental poisoning can increase when not enough Homocysteine gets converted into Glutathione.  Glutathione is responsible for detoxifying the body of the heavy metals we encounter in the environment - it is our body's most powerful antioxidant.  When a body gets too burdened by heavy metals and toxins, a lot of unexpected health problems emerge.  Some symptoms of this can be: nausea, diarrhea, abdominal pain, liver and kidney dysfunction, hypertension, tachycardia, pulmonary fibrosis, asthma, immune problems, hair loss, rashes and more.

Sometimes diseases/disorders fall under a 'two-pronged' cause, meaning the causes of it stem from both genetic and environmental problems).  Autism is a big one that falls into this 'two-pronged' cause category [American Journal of Biochemistry and Biotechnology, 2008] along with Fibromyalgia, Chronic Fatigue Syndrome and more.  MTHFR is at the top of a list of 16 genetic defects for autism.  Another study showed 98% of children with autism had one or both of the MTHFR gene defects (677 and/or 1298).  A recent clinical study indicated that mothers with MTHFR who didn't take folate during pregnancy were 7 times more likely to have an autistic child than mothers without the MTHFR gene defect [Epidemiology, July 2011, Vol. 22, Issue 4, pgs 476-485].  Colon and gastric cancers also have key links to the MTHFR gene defects, just do an internet search on 'MTHFR and colon cancer' or 'MTHFR and gastric cancer' and you will find many clinical studies and articles on the subject.

 If I Have Variant Copies of the MTHFR Gene, What Can I Do?

If the MTHFR enzyme is inefficient, you can compensate for your body's inability to methylate efficiently since this biological process is dependent on several B vitamins.  You may simply need more B vitamins than someone without a variant copy of this gene, such as vitamin B6, B12 (methylcobalamin) and the active form of folate (5-methyl tetrahydrofolate).  Other methyl donors such as SAMe and trimethylglycine may also provide benefits.  If you have a defective copy of the MTHFT gene, it is important for you to monitor your homocysteine level as well.  Fortunately, lowering homocysteine can often be done with the nutrient supplements listed above.

Determining what copies of the MTHFR you have gives you the ability to compensate accordingly.  The old paradigm that we are simply a the mercy of our genes is now challenged.  Genetic testing empowers you to take control, launching you into a new age of truly individualized healthcare.

I knew the more I researched the more I would discover.  The deeper I looked I realized how hard Emmalin's little body really has to work.  As scared as some of this makes me, I thank God I know what to do to help my child be her best.  Now most of the stuff I was already doing with Emmalin so I only have to change up a few things.  I now know what multi-vitamins she can handle and which ones are toxic to her and me.  I have always been heavy on the B Vitamins but I did need to change her B12 vitamin based on this new information.

Why MTHFR Is Only A Part of Methylation
Here is the B Vitamin that we use currently.
And here is the vitamin we are switching too:
Please watch for my next post when I go into details about the lifestyle and dietary changes I have made for Emmalin and our family, now that we know each of us is affected by the MTHFR gene.   


  1. Hi.

    For what it's worth ...

    If I may make one suggestion, the Nutrichem multivitamin contains cyanocobalamin, a vitamin B12 with a cyaninde molecule attached. The body doesn't handle this well and has to get rid of the cyanide molecule.

    Look for multivitamins with methyl-, hydroxy- and/or adenosyl-cobalamin (B12). I have an mthfr defect and our family use the Thorne Multivitamins, which come in various versions for males, females (under and over 40) and children.