Methylenetetrahydrofolate Reductase Gene Mutation

The MTHFR gene mutation (and other methylation dysfunction states) is a genetic weakness with profound health implications.  It is now recognized as a relatively common genetic variant that limits vital enzyme function and is implicated as a factor in a constellation of symptoms, syndromes, and medical conditions.

In the advancement of personalized medicine, genetic testing has identified 40+ variants of the gene that encodes (holds the blueprint for making) the MTHFR enzyme.  The enzyme is the rate-limiting enzyme in the methyl cycle; the function of the entire pathway is limited by this one component.

Methylation: What is it and why does it matter?

Methylation is an essential biochemical process involving the transfer of a methyl group to a substrate.  This somewhat basic biochemical process (with a confusing description) occurs billions of times per second in the cells.  It is involved in nearly every reaction in the body and its broad function affects every system of the body.

  • Gene regulation – turning on and off of genes
  • Detoxification (or activation) – chemicals, toxins, heavy metals
  • Nerve function – protection, signal transmission
  • Immune system – development of T cells and NK cells
  • Energy production – cellular energy production
  • Hormone regulation – process hormones
  • Cognitive and emotional health – builds neurotransmitters that affect mood
  • DNA and RNA synthesis

Proper and efficient methylation is controlled by several factors including the simple availability of methyl groups to transfer.  As described, the MTHFR enzyme is the controlling enzyme in the production of methyl groups.  The essential outcome of a MTHFR gene mutation, therefore, is decreased production of methyl groups, and impaired methylation.

Signs and symptoms of MTHFR gene mutation

The interplay of the type(s) of mutation, the broad influence of methylation and the infinite elements of environmental exposure create a symptom picture that varies greatly from person to person.  The magnitude of the loss of methylation varies greatly among individuals depending on the number and type of mutations.  Impaired methylation affects every system in the body.   Lastly, an individual’s symptom picture is compounded by the interplay of their unique environmental factors that act to amplify or minimize the effects of diminished methylation.

In a simplified overview, though, you might consider three main categories that relate the symptom presentations – cardiovascular health, neurologic health and systemic intoxication (increased toxic burden).

Cardiovascular – elevated homocysteine levels (decreased conversion by methylation to methionine and then to SAMe) is related to risk of stroke, heart attack, frequent miscarriages, congenital birth defects, anemia.

Neurologic – decreased production of SAMe (from decreased methylation of homocysteine) leads to decreased production of dopamine, serotonin and norepinephrine, all responsible for mood.  Conditions may include depression, alcoholism, aggression, Autism, fatigue, fibromyalgia, chronic fatigue syndrome, bipolar disorder, Obsessive Compulsive Disorder, Alzheimer’s disease, Dementia.

Systemic intoxication – build up of toxic metabolites cause damage to the organs of elimination: liver, skin, kidneys, colon, lungs.  We see conditions like nausea, diarrhea, pulmonary fibrosis, immune dysfunction, hair loss, kidney and liver dysfunction, colon cancer, rashes, rapid heart rate, high blood pressure and more.

MTHFR and Related Health Conditions

MTHFR Testing and Results

Genetic testing is required to identify or rule out this essential underlying factor as a cause of diminished methylation. Genetic testing for MTHFR reviews specific positions on the DNA strand that encode the MTHFR genes.  A simple base change (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 methyl groups for methylation.   You have two copies of your DNA that encode the MTHFR enzyme.  This extra copy serves 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 decreased methyl group production.   Double copy errors are more significant and are far more likely to result in impaired health.

As discussed, there are over 40 variants in the MTHFR gene.  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 both copies of DNA to identify any copy errors – single (heterozygous) or double (homozygous) copy errors.  Loosely, the C677T mutation is associated with cardiovascular events while A1298T is associated with neurologic conditions.  Systemic intoxication results from the decreased methylation central to the processing and detoxification of heavy metals, medications, chemicals, etc….

You can ask your physician to order the MTHFR gene mutation test on routine screening labs. However, we highly recommend going a step further and having a detailed genotyping test via 23andme. The raw data from this test, will give you over 300 variants, 19 pages of information, including the MTHFR mutation. Once you receive your results, you can schedule a consult with Dr. Sherri to interpret the data and apply it to your individual health concerns and goals.

MTHFR: Approach to Care

The management of MTHFR can be as complex as individuals are unique.  The type and number of mutations can greatly affect the approach to care and its outcome.  Generalized care aims to restore and optimize the production of methyl groups while decreasing the overall depletion.  We cannot change our genes but we can change how they act.  This essential approach requires a comprehensive diet and lifestyle approach that addresses the drains and provides adequate support to proper and efficient methylation.  Supplementation with specific nutrients is essential but complex.  Further genetic testing is often necessary to identify other impaired enzymes that are involved in the methyl cycle and account for how each individual responds to care.  As it is a genetic condition, family members can carry the same or similar gene mutations.  It is, therefore, recommended that family members consider testing and treatment for MTHFR gene mutations.

More Information About Methylation:

Methylation Pathways

Dr. Ben Lynch’s webinar Colleague and Leading MTHFR researcher

MTHFR Support: MTHFR Advocate Organization

HealthE Coaching Methylation Blogs:

Do I Look Healthy In These Genes?

Breast Health and Epigenetics

If I Had to Start the Aging Process All Over Again, I Would….

Supplements- Should You Be Taking Them?

Guide to Understanding

And don’t forget to check out our Free MAD DOC supplement guide created specifically with methylation in mind.



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