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MTHFR and the Magic Purple Pill

Note: This post is from 2010, and some of the information is now out of date. When this was written there were very few genomic tests available, methylated folate and B12 supplements had not yet been created and these molecules were only available as high dose prescriptions. Our understanding and approach to genomics has evolved a lot. Please see more recent MTHFr posts for up to date information. I have included this post as a historical archive.





The missing link for depression, fibromyalgia, IBS and more. MTHFR is shorthand for a specific gene that codes for an enzyme called "Methyl Tetra Hydro Folate Reductase". This enzyme adds a methly group to a folate molecule.


The web of biochemical reactions in the body is dense and complex, but there are a few spots that are what I would call "bottlenecks" where a single wrench can shut down many engines. This particular enzyme (MTHFR) is responsible for adding the methyl group that feeds the "methylation cycle". The methylation cycle is best known for changing homocystiene into methionine, but it also impacts many, many enzyme systems in the body. Methylation is involved in the production and break down of brain chemicals such as serotonin, dopamine and norepinepherine. It affects enzymes that are involved in energy production. It is also involved in glutathione production. Gluathione is a pivotal anti-oxidant molecule involved in our natural detoxification process.


There are 31 known variations of the MTHFR gene. The two most common are known as the 677 and the 1298 (which makes reference to the specific location on the gene wher the change is). These variants produce a MTHFR enzyme that is 30-60% less active than normal. As with all genes, MTHFR comes in pairs. You get one from each parent - which is why we see some of the symptoms of MTHFR running in families. Since there are 2 copies it is possible to have:

  • Two normally functioning genes

  • One normal gene and one slower gene

  • Two genes that are the same low functioning variant

  • Two genes that are different low functioning variants


Having one or two of the lower functioning variants can contribute to:

  • High Homocystiene which increases risk for

    • atherosclerosis

    • stroke

    • blood clots

  • Folate deficiency related pregnancy issues

    • miscarriage

    • pre-eclampsia

    • neural tube defects (cleft lip, cleft palate, spinabifida)

  • Neurotransmitter imbalances such as

    • Depression

    • Anxiety

    • Insomnia

    • Addiction

  • Significant decrease in ability to eliminate toxins which contributes to

    • high oxidative stress

    • immune imbalance

    • hormone imbalance

    • neurological symptoms

    • cancer risk


All of the above contribute to the development of complex, chronic disorders such as:

  • IBS

  • Chronic Faigue

  • Fibromyalgia

  • Dementia

  • Schizophrenia

  • Parkinson's

  • Autism



Testing for MTHFR requires a simple blood test, and is covered by most health insurance. The good news is the enzyme deficiency is correctable using a special form of folate (available by prescription). Many patients that have these less-than-optimal genes experience significant (and sometimes dramatic) improvement once beginning the "MTHF Repletion" protocol. The protocol is simple and affordable.


Oh, and why the "Magic Purple Pill"? One of the 3 prescriptions containing methyl folate is a purple color, and several of my patients have called it "the magic purple pill".


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