Methylation

Written by Phoebe Wynne-Lewis, BHSc, Dip Nat Med, Dip Herb Med – FxMed Technical Support

What is Methylation?

Methylation is a vital metabolic process that happens in every cell and every organ of the human body, taking place a million times a second. Life would simply not exist without it. Think of billions of little on/off switches inside your body that control everything from your stress response and how your body makes energy from food, to your brain chemistry and detoxification. That’s methylation.

Methylation is the transfer of a methyl group (1 Carbon atom & 3 Hydrogen atoms) onto amino acids, proteins, enzymes and DNA. The addition of a methyl group onto these molecules facilitates biochemical reactions vital to critical functions in our body such as: thinking, repairing DNA, turning on and off genes, fighting infections and detoxification (especially in the liver). It is also important for the proper functioning of the Hypothalamic-Pituitary-Adrenal (HPA) axis and critical for the synthesis of all neurotransmitters and histamine; for example, the enzyme that converts norepinephrine to epinephrine is dependent on methylation for activation.

Why should we be concerned about Methylation?

Methylation is involved in the following:

  • 400 + enzymatic & cellular reactions
  • DNA synthesis & repair
  • Cell replication & repair
  • Neurotransmitter synthesis & metabolism
  • Energy production/metabolism
  • Hormone regulation
  • Detoxification
  • Epigenetics – gene expression/regulation
  • Telomere Integrity
Methylation turns genes on and off

When a molecule receives a methyl group, this “starts” a reaction (such as turning a gene on or activating an enzyme). For example molecules receiving methyl groups “turn on” detox reactions that detox the body of chemicals, including phenols. So if you are phenol sensitive, and increase your methylation, then theoretically your body can process more phenols and you can eat high phenol containing fruits without enzymes!

Another example is molecules receiving methyl groups “turn on” serotonin, and thus melatonin, production. Therefore, if you are an under-methylator, you can increase your methylation and have higher levels of serotonin and melatonin. This may mean reducing SSRIs, or having improved sleep.

When the methyl group is “lost” or removed, or if we are short of methyl groups, the reaction stops. When we are short of methyl groups our body cannot respond to the nutrients, vitamins, minerals or herbs we ingest, affecting many biological reactions in the body.

There are four cornerstones to the methylation cycle – Methionine, (SAMe), S-adenosylhomocysteine, Homocysteine.
There are important co-factors that allow the methylation cycle to function including the B vitamins i.e folate, B12 and B6. These B vitamins have to be in their activated form, namely Methylcobalamin, Folinic acid, 5 MTHF and Pyridoxyl-5-Phosphate.

Why does our Methylation Cycle not function properly?

Our methyl groups e.g. choline, methionine, MTHF, B6 and B12 may not be working properly due to:

  • A genetic mutation e.g. MTHFR.
  • Shortage of methyl groups – from environmental pollutants like Bisphenol A in plastics, chemicals & heavy metals such as lead, mercury, cadmium (from smoking).
  • Diet – humans ingest approximately 50 mmol of methyl groups per day; 60% of them are derived from choline. When they are deprived of choline, they use more methyl groups from folate, increasing dietary folate requirements. Conversely, when they are deprived of folate, they use more methyl groups from choline, increasing the dietary requirement for choline.
  • Stress – if the stress response is using up the methyl groups then this shortage will affect other organs like the brain, thyroid, adrenals & pancreas.
  • Aging – methyl groups decline with age. So cognitive decline can be greater if we have a decrease of methyl groups.
  • Infections – viruses/bacteria, fungi.
  • Alcohol – the ethanol in alcohol inhibits methylation.
  • Medications e.g. antacids, methotrexate – can hinder the methylation pathway.
Methyl- Related Foods
  • Folate – strawberries, citrus fruits & leafy green vegetables.
  • Vitamin B12 – fish, meat, milk & eggs.
  • Choline oxidizes to form a source of methyl called Betaine – which is found in beef liver, toasted wheat germ, eggs, cod, beef, brussel sprouts, broccoli, shrimp & salmon. Two large eggs contain 252mg choline, nearly half of the recommended 550mg per day for men.
What is MTHFR?
  • An enzyme that adds a methyl group to folic acid to make it usable by the body.
  • The MTHFR gene produces this enzyme that is necessary for properly converting folic acid to its active form 5MTHF. This enzyme is also important for converting homocysteine into methionine.
  • Activated folate (5MTHF) goes on to give its methyl group to other nutrients & substances – “methylation.”
  • 5MTHF is required for the creation of every cell in our body, and also used to create neurotransmitters (serotonin, epinephrine, norepinephrine & dopamine); create immune cells; process hormones (i.e estrogen); as well as to produce energy & detoxify chemicals.
MTHFR Gene Mutation
  • Those with a defective MTHFR gene have an impaired ability to produce the MTHFR enzyme (estimates range from 20%-70% or more). This can make it more difficult to break down and eliminate substances like heavy metals.
  • Individuals with the MTHFR gene mutation have difficulties processing B9 in the form of folic acid (commonly present in supplements and added to processed foods). This type of B9 may even cause a build-up in the body leading to toxicity which can raise levels of homocysteine.
  • Elevated homocysteine levels are associated with a higher risk of heart disease, inflammation, birth defects, difficult pregnancies, and potentially an impaired ability to detoxify. This also affects the conversion to glutathione, which the body needs to remove waste and which is a potent antioxidant.
  • Many factors can contribute to the expression of the MTHFR mutation including; our environment, foods, chemical exposure & stress.
How do we get this Mutation?

The reason for the types of mutations is variations in the specific genes passed on from each parent. In other words, if both parents pass on a healthy gene, a person won’t have a mutation at all. If one parent passes on a healthy gene but the other passes on a mutated gene, several variations can occur. If both parents pass on a mutated form, there are many more scenarios that can occur.

The two most problematic mutations in the MTHFR gene that can occur are the following SNP’s: C677T
and A1298C. While a ‘normal’ MTHFR gene would be C 677C (c= cytosine), a mutation has made the
gene C 677T (t= thymine). The letter represents the nucleotide base and the number refers to the location of the mutation on the gene.

The most common forms of MTHFR mutation involve various combinations of these genes being passed on from each parent:

  • Homozygous: the same gene passed on from both parents – can occur if both pass on the 677
    mutation or the 1298 mutation.
  • Heterozygous: one parent passed on the 677 mutation or the 1298 mutation but the other parent
    passed on a normal gene.
  • Compound Heterozygous: one parent passed on the 677 mutation and the other passed on the
    1298 mutation.
What is a SNP?

When the methylation cycle does its job it supports a wide range of bodily functions. But when SNPs are present in key places in the cycle, they can cause an over or underproduction of certain chemicals, undermining the task of methylation.

SNPs (Single Nucleotide Polymorphisms) are the most common type of genetic variation among people. Each SNP represents a difference in a single DNA building block, called a nucleotide. For example, a SNP may replace the nucleotide cytosine (C) with the nucleotide thymine (T) in a certain stretch of DNA. Commonly tested SNPs include; MTHFR C677T & MTHFR A1298C.

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