WHAT IS METHYLATION?
Methylation is a chemical reaction that occurs in every cell and tissue in our body. Chemically speaking, it is the process of adding methyl groups to a molecule. (A methyl group is a chemical structure made of one carbon and three hydrogen atoms.) Since methyl groups are chemically inert, adding them to a protein (the process of methylation) changes how that protein reacts to other substances in the body, thus affecting how that protein behaves. Enzymes, hormones, and even genes are proteins, and the process affects them all.
In some ways, the methylation of proteins helps the body detoxify. For example, the methylation process helps convert the toxic amino acid (homocysteine) into a beneficial amino acid (methionine). If your body cannot methylate properly, toxins build up in your bloodstream and will eventually cause disease.
Another role of methylation is to help the enzymes in our bodies work efficiently. Enzymes are proteins that act as switches for chemical reactions – they initiate essential processes in every cell and tissue. In a similar way, methylation affects our genes, which are also made up of proteins. Methylation can turn genes on or off, which can be good or bad for our health, depending on the gene.
Some nutrients affect the process of methylation quite dramatically. Methyl donors donate methyl groups to proteins and methylating factors (nutrients like vitamin B12 and zinc) help this process along by monitoring specific methylation reactions. How well your body can methylate is important to your overall health.
Methylation Regulation and Distribution
HOW IS METHYLATION REGULATED?
Methylation is regulated by Enzymes and Substrate (end product)
1. Many enzymes require cofactors for activation, and these cofactors are derived from vitamins or minerals.
2. Cofactors are required to complete the process
3. Cofactors are required to turn off methylation
4. Excessive substrates may turn off methylation (feedback inhibition)
HOW IS METHYLATION DISTURBED? METHYLATION IS OFTEN DISTURBED BY VARIOUS MECHANISMS
1. Genetic mutations
2. A lack of cofactors driving methylation forward (e.g., zinc, magnesium, and B6)
3. Medications (e.g., antacids)
4. Specific nutrients depleting methyl groups (e.g., niacin)
5. Environmental toxicity, heavy metals, chemicals (e.g., acetaldehyde, arsenic, and mercury)
6. Excessive substrate (feedback inhibition)
7. The lack of sufficient methyl donors requires more specific medications, such as methotrexate
WHAT IS MTHFR?
• MTHFR is an enzyme responsible for converting 5,10-methylenetetrahydrofolate to the product 5-methyltetrahydrofolate. It is involved in the metabolism of folate and homocysteine.
• The product of the reaction catalyzed by MTHFR converts homocysteine (a potentially toxic amino acid) to methionine (a useful and necessary amino acid).
WHY IS MTHFR GENOTYPING IMPORTANT?
• Certain mutations in the gene coding for MTHFR produce an enzyme that has reduced activity.
• Reduced activity diminishes your overall ability to methylate, which affects all cells in your body, including the expression of your DNA.
• Reduced activity can lead to elevated levels of homocysteine (a.k.a. hyperhomocysteinemia), especially when folate levels are low.
• High homocysteine (>13umol/L) may double the risk of developing illness or complications.
• MTHFR genotyping can provide information about potential causes of elevated homocysteine and approaches for addressing it.
• Based on MTHFR and homocysteine results, physicians can develop dietary and medical recommendations.
• Discovering your MTHFR genotype can provide valuable information about how to support your biochemical pathways to facilitate optimum health.
• An increased intake of 5-methyltetrahydrofolate alone or in combination with methyl B12 and B6 is recommended.
• Based on the results, recommendations for methotrexate dosage can be adjusted.
WHAT MEDICAL CONDITIONS MAY BE AFFECTED BY VARIANT COPIES OF THE MTHFR GENOTYPE?
IF I HAVE VARIANT COPIES OF THE MTHFR GENE, WHAT CAN I DO?
Nutrition plays a substantial role in methylation pathways. You can compensate for your body’s inability to methylate efficiently since this biological process is dependent on several vitamins. You may need more B vitamins than someone without a variant copy of this gene, such as B6, methyl B12, and the active form of folate. Other methyl donors such as choline, SAMe, and trimethylglycine (betaine) may also provide benefits. If you have a variant copy of the MTHFR gene, it is important to monitor your homocysteine level as well. Fortunately, lowering homocysteine can often be done with the nutrient supplements listed above.