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MTHFR is the tip of the iceberg in relation to your methylation abilities. Knowledge regarding the MTHFR mutation is changing rapidly. I recently attended the Annual Conference of the Institute of Functional Medicine where I heard from methylation experts and researchers. They 23andmediscussed implications, treatment options, and other factors that influence your ability to methylate. The MTHFR mutation has stirred up a national “craze” about methylation, and the MTHFR Mutation itself has reached Celebrity Status.   If anyone knows one single gene mutation (or SNP) in the entire human genome, it is likely to be the MTHFR mutation. However, this is just the beginning – you are looking at the tip of the iceberg.

For instance, many practitioners, including myself, have been using homocysteine levels to determine the dose of L-Methylfolate (MTHF, 5-MTHF, L‑methyltetrahydrofolate, Deplin) to be given. However, we now know that homocysteine can inappropriately exit too quickly through a mutation of the CBS enzyme. This mutation causes a false reassurance of a “normal” homocysteine level. The enzyme CBS dumps Homocysteine out of the cycle (see figure). The whole purpose of Homocysteine is to generate Methionine and Glutathione, which aid in antioxidant production. While it is true that elevated homocysteine raises your risk for heart disease, inadequate, or low, homocysteine levels can theoretically cause the same risk since the goal is to produce antioxidants.

23andme - methylation

We now know that there are multiple mutations that play supportive roles in your methylation process. It is not all about MTHFR anymore. If you look at the diagram, you will see multiple mutations that revolve around Methionine production: MTR, MTRR, TCN2, FUT2, COMT, and CBS. If you have kinks in the pathway, you can take mega doses of L-Methylfolate without actually creating Methionine since you lack other key ingredients. These other mutations effect how you process your other B vitamins. For example, certain mutations require Methylated B12 while other mutations prefer Adenosyl B12.

Getting all of these genes tested individually can be quite costly. Prices range around $100 per gene through local lab companies like Quest, CPL, and LabCorp. I just listed 6 genes, which would cost $600. However, there might be 20 genes involved in a few years! This is why I am now encouraging all of my patients to get their entire human genome sequenced.

23andMe is a genome sequencing service. They are currently the most popular and cheapest. It currently only costs $99 to get your entire genome sequenced, and it will give you a list of every gene and mutation that you have. Your genome never changes – it is identical from birth to death. Therefore, with your genome fully sequenced, we will be able to apply new knowledge as it evolves.


Once you have your genome sequenced, it is important to get clinically useful information out of your DNA. The ancestry data is fun and interesting, but we recommend PureGenomics.com (free service) to our patients as PureGenomics is compiling clinically relevant data regarding your methylation pathways, and they will constantly update the database as new research is released. Their report will advise you, and your practitioner, how to best structure a treatment regimen to get the most out of your methylation pathways.


At this time, PureGenomics can only be accessed through healthcare practitioners that are signed up. In order to be invited, just send us an email. It is a free service provided by Pure Encapsulations.

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I am frequently asked how much methylfolate and B12 to consume. Without knowing your personal SNPs, or mutations, I would recommend small amounts of methylfolate and methylcobalamin (B12) with additional cofactors. My two favorite products at this time are PhytoMulti and Glycogenics taken twice daily. Both of these are available at our office.