MTHFR is an enzyme in the methylation cycle that converts 5,10MTHF to 5-MTHF Methylene-tetrahydrofolate reductase, basically the conversion of inactive vitamin B9 to active vitamin B9. The MTHFR enzyme is vital for many biochemical processes in the body and is a major player in the methylation cycle. A genetic problem interferes with your body’s ability to break down folates and folic acid into methylfolate, leading to a decrease in methylfolate production, methyl B12 production, and SAMe (S-Adenosyl Methionine). Deficiencies in active folate (methylfolate) can cause many chronic neurological and metabolic health conditions.





What are the MTHFR Genetic Defects?

There are various polymorphisms (or SNPs) that can occur on the MTHFR gene, they are named for the number position on the gene. The letters stand for one of the nucleobases (Guanine, Adenine, Thymine, Cytosine). The two most common genes that have been extensively researched by Ben Lynch and Amy Yasko are the C677t and the A1298c.  The C677t is more commonly associated with the re-methylation of homocysteine in the methionine cycle.  The A1298C is associated with neurotransmitter activity through the BH4 cycle.

How do we know if the gene has expressed itself?  History, symptoms and objective testing with the Organic Acids Test allows us to accurately determine if it has expressed.  High FIGLU suggests a tetrahydrofolate deficiency.

Although MTHFR is the cornerstone of several important pathways there is much more to interpreting and personalizing a nutrition plan for the patient.  Dietary intake of green leafy vegetables that are high in folate will help but we must look at the entire cycle and support the pathways necessary to regain health.


Common MTHFR Genetic Mutations

  • Heterozygous +/- — 30-40% reduction in MTHF production
  • Homozygous +/+ — 70-75% reduction in MTHF production

  • Heterozygous +/- — 10-20% reduction in MTHF production
  • Homozygous +/+ — 30-40% reduction in MTHF production

Compound Heterozygous (677/1298)
  • 40-60% reduction in MTHF production
  • (Heterozygous – one normal gene, one affected gene)
  • (Homozygous – one gene from mom, one gene from dad)



Within the folate cycle is the gene MTHFR.   A mutation or gene variant at this position can affect the methylation cycle and the production of methionine.  Methionine is important for the production of SAMe, an important methyl donor and phospholipid metabolism.   Also within the methionine cycle is the production of Homocysteine via the AHCY gene and BHMT, which re-methylates homocysteine into methionine.  Another SNP that can affect this cycle which needs to be adressed is the MTRR which methylates B12 and re-methylates homocysteine into methionine.  The MTRR gene works synergistically with MTR.

MTHFR also directly impacts the BH4 cycle, which affects our neurotransmitters.

COMT degrades catecholamine neurotransmitters, dopamine, norepinephrine and epinephrine.

VAl158 regulates dopamine in the frontal lobe.

MAo-A has been shown to degrade serotonin which is an important marker for depression.  It has also been associated with aggression and anti-social behavior.  It has been found that progesterone therapy has been beneficial in woman with this genetic mutation.

MAo- B  This has been shown to correlate more with clinical depression

GAD 1,2  Decreased conversion of glutamic acid to GABA.  Associated with sleep disorders, low muscle tone and spasticity

AHCY 1,2,19 Homozygous will lower homocysteine and glutathione

CBS c699t Homozygous will lower homocysteine and glutathione

SOD 1  Been found to affect the cytoplasm and mitochondria

NOS 1 Decreased ability to metabolize nitric oxide

NAT2 Homozygous can cause chemical avoidance

VDR Homozygous results in decreased activity in receptor that transports Vitamin

FOLR1 Primary folate receptor for cells.  ***presence can cause a methylation deficiency without having an MTHFR

As previously stated not all genes express themselves so we coordinate the information with data from the Organic Acids Test.  High VMA suggest norepinephrine breakdown, HVA is a metabolite of dopamine and HIAA breaks down serotonin.

MTHFR, or 5 ,MTHF is also a promotor of Nitric Oxide Synthesis which is essential for artery elasticity.

PEMT is essential for phospholipid metabolism

GAMT suggests creatine deficiency and an excess has major implication on muscle health tissue and aberrant methylation


It is extremely important to look at the entire picture and not just the MTHFR.  


The more polymorphisms, typically the more significant the problem.

Its all about making Glutathione and SAMe, the body’s key antioxidant and methyl donor respectively. MTHFR mutations cause low Glutathione, causing more toxicity and higher oxidative stress – chronic neurological and metabolic conditions.


MTHFR Mutation Statistics
  • Over 70% of children with Autism Spectrum Disorders have MTHFR mutations
  • Over 60% of mothers who gave birth to a child with Down Syndrome have MTHFR mutations
  • Approximately 45% of the population has 1 copy of the MTFHR C66T genetic mutation


Addressing MTHFR & Other Methylation Mutations

Supplement with what your body isn’t creating. Based on genetic testing, one can determine what is needed to bypass or support a specific mutation or SNP, as well as determining if any additional cofactors or substrates are needed

  • Remove underlying chronic infections such as: Lyme, bacteria, viruses, parasites, and yeast
  • Address Heavy Metal Toxicity
  • GI function & Detoxification is key
  • Follow up testing and monitor improvement

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