March 25, 2012


MTHFR stands for the mehylenetetrahydrofolate reductase gene.  It is located on chromosome 1 and is responsible for making the MTHFR enzyme.  This enzyme is essential for processing amino acids.  Specifically, it converts folate (vitamin B9) into a usable form (converting 5,10-methylentetrahydrofolate to 5-methyltetrahydrofolate) which is needed in the reaction to convert the amino acid homocysteine to methionine. It is also needed to make neurotransmitters (dopamine, norepeniphrine, serotonin) and glutathione (which is your body’s main detoxifier). Excessive homocysteine (hyperhomocystenima)  can lead to cardiovascular disease and thrombosis (to name just a few problems) and is often associated with infertility.

There are (at least) 40 genetic polymorphisms in the MTHFR gene.  These polymorphisms reduce the enzyme’s activity.  The two most significant ones are the C677T and the A1298C, or the T and A mutation for short.  In these two mutations, Cysteine is replaced with Thymine and Alanine is replaced by Cytosine, respectively.  A person can be either heterozygous (one normal, one variant) or homozygous (two affected genes) for either or both of these mutations. The homozygous T mutation occurs in roughly 5-10% of the general population, and the A mutation in 30-50% of the population.  This is a very common problem and most labs can now run this simple test.  With a homozygous mutation, anzyme efficacy drops to 10-30%; the heterozygous mutation is about 60-70% as effective.   What this translates into is that roughly 10-12% of the population cannot metabolize folic acid and 40-44% of the general population is limited in their ability to utilize folic acid.   When you look at some specific subpopulations, the implications are profound:   70% of people with major depression have a T mutation;  roughly 98% of autistic children have an MTHFR mutation.    Autism is not as simple as this polymorphism, but it certainly could be a significant contributing factor when one starts to think about the role of toxicity, such as mercury exposure, and the body’s diminished ability to clear toxins with reduced glutathione.

Fortunately, this mutation, and its subsequent deleterious effects, can be bypassed by using a methylated form of folate (l-methylfolate), which readily crosses the blood-brain-barrier.  One version of this is Deplin by Pamlab, who has also manufactured a generic version of this medical food (it’s technical classification by the FDA).  L-mthylfolate has become a fantastic augmentation strategy in treating depression and anxiety (when the standard SSRI alone doesn’t cut it), and will likely prove an effective first line remedy in treating multiple illnesses- basically any illness that results from toxicity (lack of glutathione), inflammation, and neurotransmitter dysregulation- in theory, all of modern mental illness.