MTHFR: Emerging care.

In the advancement of personalized medicine, diagnosis of disease has entered the realm of genetic testing. MTHFR gene mutations and other methylation dysfunction are a significant health issue today that affect millions of people, however, sadly it is largely ignored.  At present there is a general shortage of understanding of the condition and a greater deficiency of understanding as to its management.  As an early adopter of its prevalence and importance I will concede that there is still much to be learned and, as yet, there is no universal magic bullet for it’s management.

If you or a loved one have identified a MTHFR gene mutation, either C677T or A1298C, or even both, you can remain hopeful as there is much to be done to improve your health, even resolve your signs and symptoms.  You have arrived at one of the few places that specializes in its comprehensive management.

Methylation – What? Huh?

Methylation is the biochemical process of donating a methyl group to a substrate.  Improper, poor or inefficient methylation caused by MTHFR gene mutations or other dysfunction can compromise multiple biochemical pathways and systems of the body compounding the effects and confusing diagnosis and care.

Methylation is involved in the proper and efficient function of:

  • Gene regulation – turning on and off of genes
  • Detoxification (or activation) of chemicals and toxins – both “foreign” and “domestic”
  • Nerve function – protect nerves, and signal transmission
  • Immune Function – development of T cells and NK cells
  • Energy production – cellular energy production, ATP, CoQ10
  • Hormone regulation – process and detoxify hormones
  • Cognitive and Emotional Health – builds neurotransmitters
  • DNA and RNA synthesis

Methylation is a relatively simple process within the universe of biochemistry.  Biochemistry is the study of the interactions between substrates (basic elements in the body), enzymes and cofactors within the body.  Methylation occurs rapidly in the complex soup of compounds in the body and is regulated by the presence or absence of methyl groups, various substrates, enzymes and cofactors.  Deficiency or excess of any of these components act to amplify or inhibit the function of the pathway or system.  The signs and symptoms that result depend on which pathways or systems (described above) are affected.  (Most practitioners only get this far – clearly it’s important but the implications and management get murkier.)

Methylation dysfunction: Why? How?

So… proper and efficient methylation is limited by deficiency or excess of methyl groups, substrates, enzymes and/or cofactors.  Here’s an example most of us can at least relate to for understanding this interplay.  For your car engine to start there must be an appropriate mix of oxygen, spark, fuel and timing.  Inside the engine, each ingredient depends on several conditions and for ignition to occur they need to come together correctly.  Lack of or excess of any ingredient makes itself known with a failure of the ignition system and you’re calling for a towtruck.  So, it is with methylation.  There is some leeway in the requirements for adequate methylation, however, a sustained decrease in methylation can lead to pathway or system failures; that’s when we get the signs and symptoms.

Methylation is limited by various mechanisms including lack of cofactors (vitamins and minerals), depletion of methyl groups (increased use or decreased production), excess end-product (like a dam blocks up a river), or genetic mutations (like MTHFR gene mutations).

Factors that affect, consume or inhibit methyl groups or cause methylation dysfunction:

  • Intoxication (Medications, Alcohol, drugs, Niacin, acetaldehyde)
  • Poor nutrition (Low Magnesium, Zinc, B6, B2, B12)
  • Environmental toxins (Chemical exposures are pervasive in air, water, soil, food, at home, work, school)
  • Heavy metals (Arsenic, Mercury, etc…)
  • Gene mutations (C677T, A1298C, other essential enzymes)
  • Stressors (work, mental/emotional demands, decreased sleep, you name it)
  • Excessive end-product (feedback inhibition)

Genetic testing for MTHFR mutations.

The significance of proper methylation can’t be overstated and a comprehensive lifestyle approach must be taken to address all aspects that inhibit proper and efficient function.  Genetic testing is required to identify or rule out essential underlying factors that cause decreased methylation.  Impairment in the enzymes that synthesize the nutrient methylfolate can significantly reduce the delivery of methyl groups necessary for methylation to occur.

Genetic testing for MTHFR reviews specific positions on the DNA strand that encode the MTHFR genes.  A simple base change, or single alteration in the building blocks of your DNA at one of these positions can limit your ability to create the MTHFR enzyme, and ultimately to create methylfolate, thereby significantly limiting methylation.   You have two copies of your DNA that encode the MTHFR enzyme.  This extra copy survives as a survival mechanism and allows for a backup should one copy not function.  It is important to recognize that a single copy error results in a significant decrease in methylfolate production.   Double copy errors are more serious and are far more likely to result in impaired health and disease.

Laboratory studies routinely investigate only one or two of the positions associated with MTHFR gene mutations – position 677 (most common and well characterized) and position 1298.  At each position they test for both base pairs or copies to determine single (heterozygous) or double (homozygous) copy errors.  Conditions associated with MTHFR gene mutations.

Further genetic testing.

Addressing MTHFR is complex but if it is managed well and symptoms are not improving, further genetic testing may be necessary. We highly recommend detailed genetic testing with 23andme. It is inexpensive and provides valuable insight IF you utilize the raw data from the test. This 19 page, over 300 polymorphism document will be the key to understanding your profile. Please visit What You Need To Know To Get Started