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Methylation Part 2

Proper functioning of methylation is required for our complex biochemistry to work as it should.

When we have environmental or epigenetic stressors it may cause these methyl groups to be depleted, requiring more methyl donors to fill the tank.

When one approaches methylation issues, you must be aware that adding methyl donors is like adding fuel to a fire. So, if someone is “on fire” in terms of inflammation it may first be necessary to lower the inflammation before adding methyl donors.

It should be noted that there are 2 periods in a person’s life where they have increased requirements due to growth, hormone production, and aging. Most people’s methylation requirements go up from puberty until about age 25 due to rapid brain growth and development, and then again as we enter our later years, typically beginning around age 50-60.

It is during the teens and early twenties where young people may fall into periods of depression, anxiety and attention problems that may have them reaching for self medication solutions like drugs and alcohol. Identification of these methylation issues may help to appropriately supplement the diet.

Methylation and Mood

Folic acid (a synthetic supplement) is converted to monoglutamate entities in the wall of the intestine. Once absorbed, these monoglutamate entities are then converted to methylenetetrahydrofolate. This form of the vitamin is able to enter the brain to enable neurotransmitter synthesis of dopamine, epinephrine, and norepinephrine. Dopamine is the brain chemical responsible for executive function, multitasking, pleasure and reward.

In a normal person, ingestion of folate from the diet or folic acid from supplements will supply the brain with enough methylenetetrahydrofolate to maintain an adequate supply to keep these neurotransmitters in balance. However, people with mutations such as MTHFR C677T are less efficient at making the enzyme methylenetetrahydrofolate reductase, meaning they are not as efficient at making this compound to make their dopamine. This can then lead to a deficiency that may lead to depression, for example. There are other limiting steps in this pathway, but basically when one has single nucleotide polymorphisms (SNPs) or mutations in how these enzymes are coded the conversion is less efficient, leading directly to symptoms of sadness, lack of focus, or inability to concentrate, for example.

Administration of folinic acid or methylenetetrahydrofolate or methyl folate may show significant improvement in these individuals. However, the brain is a complex interplay of electrical impulses, overlapping synapses, neural networks, and inflammatory signaling. Very often, it is necessary to take into account the degree of inflammation, for example from a virus or traumatic brain injury. For some, the addition of methyl folate too soon or in too high of an amount may cause such massive dopamine fluctuations that the brain can’t handle the feeling and the person winds up feeling worse. Some who practice nutrigenetics call this “overmethylation”. I do not see it as such. It is widely known that a certain percentage of people will have an “over inflammation” reaction to the addition of methyl donors like methyl folate. It is important to keep in mind that there are so many other SNPS we can look at in terms of nutrition to help someone lower inflammation and “clean” themselves or “detox” before they methylate. This is why I don't use the phrase overmethylation. One just must do the work on the inflammation piece first.

And keep in mind, the energy or information for all of this is coming from the mitochondria (much more to be said about these in future blog posts).

In essence, We are a complex set of information exchange between our batteries or mitochondria (yes, the powerhouse of the cell) and our DNA. But suffice it to say, if one is able to increase their mitochondrial energy production, which can be done at any age with the proper amount of methyl donors, most of these issues of the brain, mood, and aging can be improved.

Image credit: Massachusetts General Hospital and Draper Labs [Public domain], via Wikimedia Commons

© 2020 by Courtney Hunt, MD, PC


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