Dr. Tim Jackson, Guest
Thyroid Nation

Methylation and What You Need to Know

If you follow health and wellness trends to any degree, you have definitely come across an advertisement or an article regarding the 23andme Test. This test allows for individuals to submit a saliva sample and have their genetics analyzed. Well, that’s not 100% correct. It is actually testing your EPIgenetics, which is the study of how environment, nutrition, and lifestyle affect genetic expression. Our DNA double-helix consists of 4 separate letters—A, T, C, and G—to make up our genome. Typically, A binds to T and C binds to G. When the “wrong” letter gets placed in the wrong spot, this leads to alterations in enzyme production. Remember, all genes code for enzymes. When this alphabet mix-up occurs, it is referred to as a SNP, or single nucleotide polymorphism. SNPs are different than true “mutations”. Down’s Syndrome is an example of an actual gene mutation. In other words, you can’t really alter the expression of that gene. Epigenetics refers to biochemical glitches that may be encoded in your genome, but whether or not that glitch is expressed depends on nutritional status, stress levels, toxicity levels, sleep hygiene, and environmental exposures.

There are approximately 602,000 SNPs tested by the 23andme Test. The results come in a format referred to as your “raw data”. The raw data doesn’t give us any useful, actionable information. Therefore, it is necessary to run your raw data through one of the many online apps that translate this information into a -/-, +/-, or +/+ format. A plus sign indicates a copy of the polymorphism is present. Two plus signs is referred to as being homozygous. Having a +/- designation is referred to as being heterozygous. The more copies of the SNP that you have, the greater the effect on the enzyme that it codes for. The percentage of enzyme alteration depends on the specific polymorphism in question and whether that SNP results in an up-regulation or a down-regulation of the enzyme. Again, depending on the SNP, dietary and lifestyle changes may be needed, along with targeted supplementation. Most of the reports available online analyze polymorphisms related to methylation (MTHFR), estrogen balance, ability to process Vitamin A and Vitamin D, ability to detoxify, and much, much more.

So, why should you do the test? Why should you care about the results? Because it empowers you—the client—with actionable information that can help improve your health and potentially ward off disease. Of course, the FDA prevents what claims can be made regarding the test. When you receive your final report, I highly suggest connecting with me or someone else well-versed in epigenetics to walk you through what certain SNPs mean, what further testing may be needed, what supplements and dietary changes may be beneficial, and more. So, let’s go over some of the more commonly problematic SNPs that may impact your health.

The most important and well-known polymorphism is the MTHFR SNP. Despite resembling a curse word, MTHFR stands for methylenetetrahydrofolate reductase. This enzyme works to convert inactive folate into methyltetrahydrofolate, or L-5MTHF. Actually, there are over 100 biochemical reactions that participate in a process known as Methylation. MTHFR plays a major role in this cycle. So, what is methylation? What does it do and how does it affect us? The process of methylation participates in the following:

  • Production of Carnitine, CoEnzyme Q10, and other molecules used to create energy
  • The production of myelin, the fatty covering that insulates our nerves
  • Production of certain neurotransmitters, such as serotonin and dopamine, which influence mood and happiness
  • Creating the building blocks for new DNA and RNA
  • Participating in Phase II liver detoxification of estrogens, heavy metals, nor-epinephrine, epinephrine
  • Producing SAM-e, which impacts liver and joint health
  • Maintaining the health of your cell membranes, which determines how well your cells communicate, and ultimately, how well your organs function
  • Production of bile, which is needed for fat emulsification and detoxification
  • Creation of glutathione, the body’s most powerful anti-oxidant that is also responsible for detoxing environmental pollutants, toxic metals, etc. It is also a powerful anti-viral.

As you can tell, if the methylation cycle does not work properly, our health can be severely compromised. This class of biochemical processes involves much more than just the MTHFR, which has gotten a large amount of publicity in the past 2 years. The rs number assigned to a SNP is its’ given location on the rung of the DNA ladder. SNPs will likely result in choosing an alternate amino acid, which may change the function and/or the shape of the polypeptide being coded for. As mentioned above, some SNPs will result in what is known as a down-regulation of that specific enzyme, which means it works less efficiently, and may slow down carrier protein function as well. Other SNPs will lead to what is known as an “up-regulation” of that enzyme, making it work faster and process things more quickly. The two most well-known SNPs are the MTHFR A1298C and the MTHFR C677T. Having one of those makes it difficult to convert dietary folate into the most active form. Having 2 copies—a homozygous state—will make it even more difficult to convert folic acid and folate. People with MTHFR who consume folic acid in fortified grains or supplements are causing potential undue harm to their bodies. Because they have a decreased ability to convert folic acid into the most bioavailable form, unmetabolized folic acid builds up in the blood stream. This can lead to a decreased level of Natural Killer Cells, a very important immune cell. Theoretically, decreased natural killer cells may predispose one to cancer. Metametrix offers a test that measures unmetabolized folic acid (UMFA) in the blood.

Does Methylation Have Any Impact On Thyroid Function

As a matter of fact, it does. The first one that comes to mind is that you need methyl donors to convert T4 to T3, your body’s gas pedal which affects every cell in the body. An indirect effect resides in methylation’s ability to impact serotonin and dopamine levels. Both of these neurotransmitters are needed to stimulate the production of your thyroid hormones. Another important point is that glutathione is made through the methylation process. And the thyroid gland is very sensitive to oxidative stress. So, if levels of glutathione are low, the potential for thyroid dysfunction rises. Lastly, when methylation dysfunction exists, there is a greater chance for activated viruses to be an issue. The Epstein-Barr Virus has proven to be a common culprit. One of the many things this virus can do is to trick the immune system into attacking the thyroid gland by producing antibodies to the thyroid. This process is known as molecular mimicry and can occur with other pathogens as well. The 2 markers to check would be the anti-thyroglobulin antibodies and the TPO antibodies. Many labs have reference ranges that go up into the mid-100s. However, I believe, along with many other functional wellness experts, that these numbers should be as close to zero as possible. Why would we want our immune system to have antibodies to our thyroid gland? The take home message is that your results may be within the reference range but could still be contributing to your symptoms.

We covered MTHFR and methylation in general. Now, let’s talk about another important and well-known SNP referred to as COMT, or Catechol-O-methyl transferase. Located on chromosome 22, this enzyme plays a role in breaking down our catecholamines, such as norepinephrine, epinephrine, and dopamine, as well as detoxifying estrogen. Those who are positive for COMT may be prone to higher estrogen and toxin levels, as well as stress-related neurotransmitters, dopamine, norepinephrine, and epinephrine. In short, this means those with COMT are more prone to stress and anxiety and may take longer to calm down after exposure to a stressor. As discussed with MTHFR, just because you test positive for one or for two copies of the COMT SNP doesn’t necessarily mean the associated biomarkers will be out of range. Sometimes, we can go by symptoms and a detailed history alone. Other times, we need to do some blood or urine testing. In this case, we would want to test the individual’s actual estrogen level to confirm that it is elevated. Elevated estrogen negatively affects both women and men. Women who have too much estrogen may be at risk for estrogen-associated cancers, PMS, endometriosis, fibroids, etc. Men with estrogen dominance—essentially, another way of saying too much estrogen—have increased fat around the chest area and lower abdomen. In addition, they may be unusually sensitive to comments that most wouldn’t find offensive, have a decreased libido, decreased motivation, trouble concentrating, and decreased strength. Briefly, hormones can be tested in blood, which gives us a snapshot of that person’s hormones at that exact moment in time. Another, more comprehensive, method of testing involves a 24-hour urine hormone panel. This gives us a picture of that person’s hormone levels during an entire day.


What are some actionable steps that you can take to reduce the effects of COMT on your physiology? For elevated estrogen, calcium D-glucarate works well to prevent the beta-glucuronidase enzyme from causing the body to re-absorb estrogens. Calcium D-glucarate, or CDG, keeps estrogens and toxins in the bound form, where they are then excreted through the stool. CDG will produce the best results when taken at least twice a day with food. But what can be done to lower the level of stress neurotransmitters? While a myriad of supplements and lifestyle changes can be made to modulate these levels, let’s start with the most basic. First, make sure your magnesium levels are OPTIMAL, not just normal. Magnesium should be tested through a Red Blood Cell Magnesium Test, which checks what the levels are in the actual CELLS. Blood magnesium levels are worthless, as only approximately 1% of magnesium resides here. Magnesium performs over 800 biochemical reactions, according to Dr. Carolyn Dean. One of the primary effects of magnesium is keeping the sympathetic, or fight-or-flight, nervous system from becoming over-active. An optimal RBC Magnesium Test level is 6.1 or higher. Again, we are aiming for optimal, not normal. Normal is Homer Simpson. Another stress-modulating supplement is the herb Ashwaganda. It will keep you calm and balanced, and it prevents cortisol—our primary stress hormone—from becoming too elevated. You will most likely notice that you don’t react to things that typically bother you as strongly. An important aside is that Ashwaganda increases cellular uptake of thyroid hormone. Therefore, you want to make sure you don’t develop any hyper-thyroid symptoms when starting this herb. The last supplement that I will mention for maintaining a low stress level is phosphatidylserine, or PS. PS is derived from soy and serves as 1 of 5 phospholipids that constitute the cell membrane. It helps prevent your stress hormone cortisol from increasing too much, as well as improving the clarity of your thoughts. PS helps improve the membrane health of neurons in the brain, as well as cell-to-cell communication. It is best taken on an empty stomach before an event that you predict will be stressful or in the evenings to help improve sleep.

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About the Author

Tim-JacksonDr. Tim Jackson, DPT received his undergraduate degree in Health science and chemistry from Wake Forest University in 2003. He completed his Doctorate in Physical Therapy (DPT) from the Medical University of SC in 2009. Realizing that manual therapy and orthopedic care helped only some of his patients, he began studying functional and environmental medicine, as well as digestive health, in an effort to help others achieve wellness. Dr. Tim is educated in nutritional biochemistry, digestive health and its systemic effects, as well as functional endocrinology. He recently completed the Spine portion of the Active Release Technique methodology, a system that addresses musculoskeletal trigger points and helps to expedite the healing process. Check out his website, and follow him on Facebook.

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