These are my notes for a presentation given by Dr Ben Lynch about identifying and supporting methylation issues in patients with MTHFR (which you can watch here). It is a great place to start to learn about methylation. This post covers the first 30 minutes of the presentation, which focus on methylation chemistry. The last 60 minutes is specifically about MTHFR and can be seen in this post.
What is methylation?
Methylation is basically the biochemistry surrounding the giving of a methyl group from one substance to another to alter it (a methyl group is one carbon atom with 3 hydrogen atoms attached, CH3). The recipient of the methyl group can include DNA, RNA, chemicals from our environment that have made it into our bodies, neurotransmitters and hormones, our immune system, and our nerves. For example, thymine is what you get when a methyl group is added to uracil. Without adequate methylation, there will not be adequate thymine for DNA synthesis.
The Functions of Methylation Include:
-Gene regulation (turning genes off and on)
-Transforming harmful chemicals in our bodies into less harmful and water soluble forms so that they can be excreted in the urine, or in some cases making it fat soluble and storing it in our bodies (our bodies sometimes use fat cells to store harmful chemicals until our bodies are able to detoxify them safely.)
-Making neurotransmitters and regulating their level in the blood.
-Breaking down excess estrogen.
-Building some immune cells, especially T-cells and NK cells.
-DNA and RNA synthesis
-Producing energy (CoQ10, carnitine, ATP).
-Production of myelin coating on nerves.
How Is Methylation Regulated?
It is regulated by how much substrate is available (the end product of methylation), and the amount of enzymes available. Too much of a substrate can "turn off" methylation as a feedback mechanism. Methylation is "done" by enzymes. Enzyme function may be inhibited by a lack of needed cofactors (vitamins and/or minerals needed to make the enzyme work), or because the DNA that codes for the enzyme is mutated such that the enzyme is misshapen and not able to function adequately (such as in the case of an MTHFR variance).
How is Methylation Disturbed?
-Deficiency of the vitamins and minerals that function as cofactors, such as zinc, magnesium, and vitamin B6. (This is how Pyroluria leads to under-methylation)
-Certain medications, such as antacids can disrupt methylation. Antacids casue B12 deficiency, and without adequate B12 methylation is limited.
-Some nutrients, such as niacin, use up methyl groups and thus suppress methylation.
-Environmental toxicity from chemicals such as aldehydes (common in perfumes), chemicals used in building and remodeling, heavy metals such as mercury and arsenic, alcohol, all require methylaiton to be processed so they place a strain on the methylation system. Candida (yeast) also produces acetylaldehyde and this page discusses how it interrupts methylation in more detail.
-Too much substrate limits methylation, such as too much SAM-e, or glutathione, or cysteine. All of these "shut down" methylation. This is mostly an issue from over supplementation. (People with high plasma cyteine who are mercury poisoned are often sensitive to foods containing a form of sulfur called thiols, I wonder if this is why?)
-Genetic mutations. There are many possible ones. (Yasko testing seems to me to be the best way to find out about these).
Disorders That Are Related to Under-Functioning of the Methylation System
Autism, MS, Fibromyalgia, Diabetes, Parkinson's, Chronic Fatigue Syndrome, Alcoholism and other addictive problems, ADHD, Insomnia, Alzheimer's, Cancer, Allergies, Bipolar, Schizophrenia, Depression, Anxiety, Neural Tube Defects including Spina Bifida, Cleft Palate, frequent miscarriages, Infertility, Tongue Tie, Tethered Spinal Cord, Chiari Malformation, Pulmonary Embolisms, Atherosclerosis, Immune Deficiency, Chronic Viral Infection, Congenital Heart Defects, Chemical Sensitivity, Thyroid Dysfunction, Neuropathy, Down's Syndrome, and mercury poisoning.
Why Are Disorders of Under-methylation Increasing?
-Changes in food supply resulting in less nutrition in foods and more chemical contaminants such as pesticides.
-Increased stress from fast pace of modern living (I think this is quesitonable, I think human life has always had its stresses, but I do think the modern ones are different and perhaps we are less resilient to them as we are not adapted yet).
-Our environment is saturated with chemicals- in our water, food, air, clothing, toys, electronics, cookware, etc.
-Exposures from pharmaceuticals (drugs and vaccines).
How Can Under-methylation Be addressed and Reversed?
-A multifaceted approach is needed, that looks at lifestyle, diet, environment, mental outlook, and nutrition. This is a lot, but still not enough for many people. For these people it is necessary to take genetics into account as well. He believes that MTHFR is the most common genetic cause. There are many others as well.
-The list of mutations that he has in his presentation is long, but the ones that jump out at me as likely relevant to Roo and I are GAD (which transforms glutamate to GABA), HNMT (secondary enzyme for processing histamine, after DAO), MTR/MTRR (recycling of B12), CBS (processes homocysteine), and for Roo NOS which processes ammonia, and for both of us GSTM1 which produces glutathione. This list is really worth looking at.
-As an interesting aside, he says that DAO, which is the primary enzyme that breaks down histamine, if more often damaged or down regulated by environmental factors than be inherited genetics. Alcohol in particular suppresses it's function.
