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Methylation: What is it and Why is it Important?

If you’re already following health and wellness blogs or health and wellness professionals on social media, chances are you’ve seen the word methylation. You may also see that methylation has been referenced when talking about things like genetics, Autism, insomnia, neural tube defects, and even heart disease. Methylation is a very important process in every cell in the body, but it can be difficult to understand how it all relates to our overall health. 

First, let’s define what methylation is. 

Methylation is a process that occurs in each cell to help the body make biochemical conversions. To break it down further, methylation is the act of one carbon and three hydrogens (a methyl group) attaching itself to an enzyme in the body, and then the enzyme performs a specific action. This controlled transfer of methyl groups onto proteins, amino acids, enzymes, and DNA regulates things like healing, genetic expression, liver detoxification, and immune function. You might think of it like billions of “on/off” switches inside the body that control several important functions. 

If there is a significant change to the methyl groups, the delicate methylation cycle will be disrupted and any of the involved processes can be compromised, possibly to the point of chronic conditions [1]. 

Genetics Determine How Your Body Responds to its Environment

Genes are encoded by little proteins in what is called DNA. These genes indicate things like biological traits (hair/eye color, skin tone, etc.) but they can also influence how a person’s body responds to their environment. 

Our genes provide the code for how our bodies will function, so it goes without saying that significant attention is being paid to the human genome, as well as the research about how our lifestyle factors can influence the way our genes express themselves. In other words, lifestyle factors can influence whether our genes are “activated” or “deactivated,” meaning we may have a predisposition based on our genes, but it doesn’t determine our destiny. Methylation is one of the ways that the body makes sure the right genes are turned on, and the ones that we don’t want get turned off. 

What’s MTHFR?

Gene mapping has gained traction in recent years, and one of the most well-studied genes in terms of health is methyl-tetrahydrofolate reductase (MTHFR). 

MTHFR is an enzyme that is responsible for the process of methylation in every cell, specifically one that converts folate into the active form (5-methyl-tetrahydrofolate) that can be used to make S-adenosylmethionine (SAMe), which is an important compound used in most methylation reactions. 

It’s very common to have a genetic variant that causes this key enzyme to function at a slower rate, which can negatively affect many other processes related to methylation. While lifestyle factors can significantly influence the activation of genes, some genetic mutations can influence how people respond differently to the same diet or lifestyle changes compared to someone else. While there are over 50 different genetic variants for MTHFR, the two that are most noteworthy are C677T and A1298. 

The C677T variant is one that is most commonly linked to early heart disease while the A1298C variant is associated with chronic illnesses and neurotransmitter imbalance. Either one can contribute to various health problems. These variants can also impair enzyme function to the detriment of folate utilization, which is a very important nutrient, particularly tied to the risk of neural tube defects. If you have two copies of the C677T gene (this means you are homozygous for this variant) then the MTHFR enzyme’s activity can drop by 70-75%. If you have one copy of this gene (heterozygote) then activity can be reduced by 33-35%. If you have two copies of the A1298C variant you may lose 39% of MTHFR activity. 

Another important aspect of MTHFR is homocysteine balance. When the MTHFR gene is functioning optimally, it also helps to keep homocysteine within normal levels. Homocysteine is a compound that’s often tested if someone has heart disease since higher levels have been correlated with worse outcomes [2]. High levels of homocysteine, or low levels of folate and vitamin B12, are other flags to potentially impaired methylation. 

How to Balance Methylation for Optimal Wellness

To help balance methylation, most deficits are treated by using supplemental nutrients to help improve enzyme activity. Some of the most notable nutrients are folates (5mTHF), B12, or betaine [3]. More specifically, it’s been commonly recommended that people with methylation deficiencies supplement with methylated folate (5-methyltetrahydrofolate) or methylcobalamin (vitamin B12). Because methylated folate is a normal product of the MTHFR enzyme, it works better as it bypasses the enzyme blockage. Folic acid, the synthetic form of folate, is not typically recommended for methylation deficiency as it requires further conversion in the body by the MTHFR enzyme. 

While utilizing these nutrients can be helpful for some, additional supplementation may actually lead to an increase in symptoms, especially things like anxiety, nervousness, or depression. This may be more likely if supplements are taken at higher doses for long periods of time. Perhaps more beneficial than supplementing is focusing on diet and other lifestyle factors as it can be difficult to maintain the right balance when supplementing. By consuming food-based nutrients, methylation adaptogens, following specific eating patterns, exercise, optimizing sleep and minimizing stress, it’s possible to achieve an ideal balance. You can work more closely with your functional medicine provider to determine how to support your individual methylation balance.

If you or a family member experiences any of the following conditions, it may be worth completing the MTHFR test through a genetic profile, like 23andMe

  • Addiction
  • ADHD
  • Allergies
  • Anxiety
  • Autism
  • Behavioral Disorders
  • Bipolar Disorder
  • Cancer
  • Chronic Fatigue
  • Cleft Palate
  • Dementia
  • Depression
  • Down’s Syndrome
  • Fertility Issues
  • Heart Disease
  • Insomnia
  • Multiple Sclerosis
  • Neuropathy
  • Schizophrenia
  • Thyroid Disease

Resources:
1. DNA methylation and autoimmune disease

2.  Elevated homocysteine levels and risk of cardiovascular and all-cause mortality: a meta-analysis of prospective studies.

3. Reducing mitochondrial decay with mitochondrial nutrients to delay and treat cognitive dysfunction, Alzheimer’s disease, and Parkinson’s disease.

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