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.  When a genetic problem is present, it can interfere 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 neurological and metabolic health conditions.

At Camarillo Functional Health, Dr. Michael Veselak is a Certified Functional Medicine Practitioner and Board Certified in Integrative Medicine serving in Westlake Village, Thousand Oaks & Camarillo. Throughout his experience and education, Dr. Veselak has found that dealing with complex neurological and metabolic health conditions often involves multiple factors. Working from a Functional Medicine Perspective, Dr. Veselak’s goal is to find the root cause of the condition, rather than mask the symptoms with prescription medications. This is specifically important when dealing with neurological and metabolic conditions attributed to a genetic defect.

What are the MTHFR Genetic Defects?

There are various polumorphisms (or SNPs) that can occur on the MTHFR gene, and 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 allow Dr. Veselak to accurately determine if the MTHFR gene has been expressed. For example, high FIGLU often 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 each 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 pathyways necessary to regain health. This is where the Functional Medicine approach comes into play. Dr. Michael will often order special lab tests to look further into the cause of the problem and discover where the breakdown initially occurred when treating patients near Thousand Oaks & Newbury Park. From there, he will suggest certain routes of treatment, both neurological and metabolic, to best remedy the problem.

Common MTHFR Genetic Mutations


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


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

Compound Heterozygous (677/1298)

  • 40-60% reduction in MTHF production
  • Heterzygous – one normal gene, one affected gene
  • Homozygous – one gene from mom, one gene from dad

MTHFR and MORE: Methylation Biomarkers

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 a critical componenet in 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 addressed 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.

CAl158 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. Research has been shown that progesterone therapy has been beneficial in women with this genetic mutation.

MA0-B has been shown to correlate more with clinical depression.

GAD 1,2 Decreased conversion of glutamic acid to GABA. It is also 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 has been found to affect the cytoplasm and mitochondria of the cells.

NOS1 results in decreased ability to metabolize Nitric Oxide.

NAT2 Homozygous can cause chemical avoidance.

VDR Homozygous results is decreased activity in the receptors that transport vitamins.

FOLR1 is the primary folate receptor for cells. ***The presence of FOLR1 can cause a methylation deficiency without having the MTHFR gene.

High VMA suggest norepinephrine breakdown, HVA is a metabolite of dopamine and HIAA breaks down serotonin.

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

PEMT is essential for phospholipid metabolism.

GAMT suggest creatine deficiency and an excess has major implications on muscle health tissue and aberrant methylation.

At Camarillo Functional Health, Dr. Michael Veselak stresses that it is extremely important to look at the entire picture and not just the MTHFR.  As previously stated, not all genes express themselves, so Dr. Veselak will often times recommend an Organic Acids Test to coordinate with the genetic data. The more polymorphisms, typically the more significant the problem. It’s 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 MTHFR C667t genetic mutation

Addressing MTHFR & Other Methylation Mutations

It it important to supplement with what your body is not creating. Based on genetic testing, Dr. Michael Veselak 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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